{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:33:46Z","timestamp":1793414026806,"version":"4.5.0"},"reference-count":130,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The human vascular system, comprising endothelial cells (ECs) and mural cells, covers a vast surface area in the body, providing a critical interface between blood and tissue environments. Functional differences exist across specific vascular beds, but their molecular determinants across tissues remain largely unknown. In this study, we integrated single-cell transcriptomics data from 19 human organs and tissues and defined 42 vascular cell states from approximately 67,000 cells (62 donors), including angiotypic transitional signatures along the arterial endothelial axis from large to small caliber vessels. We also characterized organotypic populations, including splenic littoral and blood\u2013brain barrier ECs, thus clarifying the molecular profiles of these important cell states. Interrogating endothelial\u2013mural cell molecular crosstalk revealed angiotypic and organotypic communication pathways related to Notch, Wnt, retinoic acid, prostaglandin and cell adhesion signaling. Transcription factor network analysis revealed differential regulation of downstream target genes in tissue-specific modules, such as those of FOXF1 across multiple lung vascular subpopulations. Additionally, we make mechanistic inferences of vascular drug targets within different vascular beds. This open-access resource enhances our understanding of angiodiversity and organotypic molecular signatures in human vascular cells, and has therapeutic implications for vascular diseases across tissues.<\/jats:p>","DOI":"10.1038\/s41591-024-03376-x","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T16:03:19Z","timestamp":1732118599000},"page":"3468-3481","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":142,"title":["An organotypic atlas of human vascular cells"],"prefix":"10.1038","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8968-4319","authenticated-orcid":false,"given":"Sam N.","family":"Barnett","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana-Maria","family":"Cujba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7045-1331","authenticated-orcid":false,"given":"Ana Raquel","family":"Maceiras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika R.","family":"Kedlian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5249-444X","authenticated-orcid":false,"given":"J. Patrick","family":"Pett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2586-9576","authenticated-orcid":false,"given":"Krzysztof","family":"Polanski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4281-614X","authenticated-orcid":false,"given":"Antonio M. A.","family":"Miranda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Cranley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumasa","family":"Kanemaru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0186-4439","authenticated-orcid":false,"given":"Michael","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Mach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shani","family":"Perera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2093-9683","authenticated-orcid":false,"given":"Catherine","family":"Tudor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philomeena D.","family":"Joseph","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Pritchard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Toscano-Rivalta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6735-6808","authenticated-orcid":false,"given":"Zewen K.","family":"Tuong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7293-0774","authenticated-orcid":false,"given":"Liam","family":"Bolt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Petryszak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Prete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4513-606X","authenticated-orcid":false,"given":"Batuhan","family":"Cakir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alik","family":"Huseynov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2242-0562","authenticated-orcid":false,"given":"Ioannis","family":"Sarropoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4204-1014","authenticated-orcid":false,"given":"Rasheda A.","family":"Chowdhury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasa","family":"Elmentaite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elo","family":"Madissoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1690-9027","authenticated-orcid":false,"given":"Amanda J.","family":"Oliver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia","family":"Campos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7298-2072","authenticated-orcid":false,"given":"Agnieska","family":"Brazovskaja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1333-0191","authenticated-orcid":false,"given":"Tom\u00e1s","family":"Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3299-5597","authenticated-orcid":false,"given":"Barbara","family":"Treutlein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7921-4447","authenticated-orcid":false,"given":"Chang N.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz J.","family":"Nowakowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin B.","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Randi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9553-5029","authenticated-orcid":false,"given":"Michela","family":"Noseda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6294-6366","authenticated-orcid":false,"given":"Sarah A.","family":"Teichmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"key":"3376_CR1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal2379","volume":"357","author":"HG Augustin","year":"2017","unstructured":"Augustin, H. G. & Koh, G. Y. Organotypic vasculature: from descriptive heterogeneity to functional pathophysiology. Science 357, eaal2379 (2017).","journal-title":"Science"},{"key":"3376_CR2","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.1002\/eji.201646789","volume":"48","author":"C Konradt","year":"2018","unstructured":"Konradt, C. & Hunter, C. A. Pathogen interactions with endothelial cells and the induction of innate and adaptive immunity. Eur. J. Immunol. 48, 1607\u20131620 (2018).","journal-title":"Eur. J. Immunol."},{"key":"3376_CR3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2217607120","volume":"120","author":"Y Qiang","year":"2023","unstructured":"Qiang, Y. et al. Microfluidic study of retention and elimination of abnormal red blood cells by human spleen with implications for sickle cell disease. Proc. Natl Acad. Sci. USA 120, e2217607120 (2023).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3376_CR4","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.tcb.2017.12.002","volume":"28","author":"A Holm","year":"2018","unstructured":"Holm, A., Heumann, T. & Augustin, H. G. Microvascular mural cell organotypic heterogeneity and functional plasticity. Trends Cell Biol. 28, 302\u2013316 (2018).","journal-title":"Trends Cell Biol."},{"key":"3376_CR5","doi-asserted-by":"publisher","first-page":"2426","DOI":"10.1016\/j.devcel.2022.09.015","volume":"57","author":"L Muhl","year":"2022","unstructured":"Muhl, L. et al. A single-cell transcriptomic inventory of murine smooth muscle cells. Dev. Cell 57, 2426\u20132443 (2022).","journal-title":"Dev. Cell"},{"key":"3376_CR6","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl4896","volume":"376","author":"Tabula Sapiens Consortium","year":"2022","unstructured":"Tabula Sapiens Consortiumet al. The Tabula Sapiens: a multiple-organ, single-cell transcriptomic atlas of humans. Science 376, eabl4896 (2022).","journal-title":"Science"},{"key":"3376_CR7","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1016\/j.stemcr.2019.04.022","volume":"12","author":"A Richter","year":"2019","unstructured":"Richter, A. et al. EGFL7 mediates BMP9-induced sprouting angiogenesis of endothelial cells derived from human embryonic stem cells. Stem Cell Rep. 12, 1250\u20131259 (2019).","journal-title":"Stem Cell Rep."},{"key":"3376_CR8","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/s44161-023-00215-z","volume":"2","author":"M Zhang","year":"2023","unstructured":"Zhang, M. et al. Tmem88 confines ectodermal Wnt2bb signaling in pharyngeal arch artery progenitors for balancing cell cycle progression and cell fate decision. Nat. Cardiovasc. Res. 2, 234\u2013250 (2023).","journal-title":"Nat. Cardiovasc. Res."},{"key":"3376_CR9","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/onc.2011.233","volume":"31","author":"M Mura","year":"2012","unstructured":"Mura, M. et al. Identification and angiogenic role of the novel tumor endothelial marker CLEC14A. Oncogene 31, 293\u2013305 (2012).","journal-title":"Oncogene"},{"key":"3376_CR10","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1161\/CIRCRESAHA.122.321692","volume":"132","author":"D Wong","year":"2023","unstructured":"Wong, D. et al. FHL5 controls vascular disease\u2013associated gene programs in smooth muscle cells. Circ. Res. 132, 1144\u20131161 (2023).","journal-title":"Circ. Res."},{"key":"3376_CR11","doi-asserted-by":"publisher","first-page":"119294","DOI":"10.1016\/j.bbamcr.2022.119294","volume":"1869","author":"Y Sato","year":"2022","unstructured":"Sato, Y. et al. Functional analysis reveals that Tinagl1 is required for normal muscle development in mice through the activation of ERK signaling. Biochim. Biophys. Acta Mol. Cell. Res. 1869, 119294 (2022).","journal-title":"Biochim. Biophys. Acta Mol. Cell. Res."},{"key":"3376_CR12","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1176","volume":"13","author":"S Sivakumar","year":"2023","unstructured":"Sivakumar, S. et al. Basal cell adhesion molecule promotes metastasis\u2010associated processes in ovarian cancer. Clin. Transl. Med. 13, e1176 (2023).","journal-title":"Clin. Transl. Med."},{"key":"3376_CR13","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1038\/s41586-020-2797-4","volume":"588","author":"M Litvi\u0148ukov\u00e1","year":"2020","unstructured":"Litvi\u0148ukov\u00e1, M. et al. Cells of the adult human heart. Nature 588, 466\u2013472 (2020).","journal-title":"Nature"},{"key":"3376_CR14","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/s41569-022-00770-1","volume":"20","author":"E Trimm","year":"2022","unstructured":"Trimm, E. & Red-Horse, K. Vascular endothelial cell development and diversity. Nat. Rev. Cardiol. 20, 197\u2013210 (2022).","journal-title":"Nat. Rev. Cardiol."},{"key":"3376_CR15","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1369\/jhc.4A6514.2005","volume":"54","author":"MP Pusztaszeri","year":"2006","unstructured":"Pusztaszeri, M. P., Seelentag, W. & Bosman, F. T. Immunohistochemical expression of endothelial markers CD31, CD34, von Willebrand factor, and Fli-1 in normal human tissues. J. Histochem. Cytochem. 54, 385\u2013395 (2006).","journal-title":"J. Histochem. Cytochem."},{"key":"3376_CR16","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/s41569-022-00805-7","volume":"20","author":"AMA Miranda","year":"2023","unstructured":"Miranda, A. M. A. et al. Single-cell transcriptomics for the assessment of cardiac disease. Nat. Rev. Cardiol. 20, 289\u2013308 (2023).","journal-title":"Nat. Rev. Cardiol."},{"key":"3376_CR17","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1016\/j.cell.2020.01.015","volume":"180","author":"J Kalucka","year":"2020","unstructured":"Kalucka, J. et al. Single-cell transcriptome atlas of murine endothelial cells. Cell 180, 764\u2013779 (2020).","journal-title":"Cell"},{"key":"3376_CR18","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1038\/s44161-023-00272-4","volume":"2","author":"M Fern\u00e1ndez-Chac\u00f3n","year":"2023","unstructured":"Fern\u00e1ndez-Chac\u00f3n, M. et al. Incongruence between transcriptional and vascular pathophysiological cell states. Nat. Cardiovasc. Res. 2, 530\u2013549 (2023).","journal-title":"Nat. Cardiovasc. Res."},{"key":"3376_CR19","doi-asserted-by":"publisher","first-page":"2189","DOI":"10.1016\/j.jacc.2020.03.018","volume":"75","author":"J Barallobre-Barreiro","year":"2020","unstructured":"Barallobre-Barreiro, J. et al. Extracellular matrix in vascular disease, part 2\/4: JACC Focus Seminar. J. Am. Coll. Cardiol. 75, 2189\u20132203 (2020).","journal-title":"J. Am. Coll. Cardiol."},{"key":"3376_CR20","doi-asserted-by":"publisher","first-page":"2106","DOI":"10.1016\/j.bbadis.2014.07.008","volume":"1842","author":"J Xu","year":"2014","unstructured":"Xu, J. & Shi, G.-P. Vascular wall extracellular matrix proteins and vascular diseases. Biochim. Biophys. Acta 1842, 2106\u20132119 (2014).","journal-title":"Biochim. Biophys. Acta"},{"key":"3376_CR21","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/j.ejphar.2010.06.066","volume":"643","author":"LSA Capettini","year":"2010","unstructured":"Capettini, L. S. A., Cortes, S. F. & Lemos, V. S. Relative contribution of eNOS and nNOS to endothelium-dependent vasodilation in the mouse aorta. Eur. J. Pharmacol. 643, 260\u2013266 (2010).","journal-title":"Eur. J. Pharmacol."},{"key":"3376_CR22","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1002\/cphy.c140049","volume":"6","author":"K Suresh","year":"2016","unstructured":"Suresh, K. & Shimoda, L. A. Lung circulation. Compr. Physiol. 6, 897 (2016).","journal-title":"Compr. Physiol."},{"key":"3376_CR23","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1161\/CIRCULATIONAHA.120.052318","volume":"144","author":"JC Schupp","year":"2021","unstructured":"Schupp, J. C. et al. Integrated single-cell atlas of endothelial cells of the human lung. Circulation 144, 286\u2013302 (2021).","journal-title":"Circulation"},{"key":"3376_CR24","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1038\/s41588-022-01243-4","volume":"55","author":"E Madissoon","year":"2022","unstructured":"Madissoon, E. et al. A spatially resolved atlas of the human lung characterizes a gland-associated immune niche. Nat. Genet. 55, 66\u201377 (2022).","journal-title":"Nat. Genet."},{"key":"3376_CR25","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/s41392-021-00762-6","volume":"7","author":"J Liu","year":"2022","unstructured":"Liu, J. et al. Wnt\/\u03b2-catenin signalling: function, biological mechanisms, and therapeutic opportunities. Signal Transduct. Target. Ther. 7, 3 (2022).","journal-title":"Signal Transduct. Target. Ther."},{"key":"3376_CR26","doi-asserted-by":"publisher","first-page":"5073","DOI":"10.1038\/s41467-020-18756-3","volume":"11","author":"SM Theparambil","year":"2020","unstructured":"Theparambil, S. M. et al. Astrocytes regulate brain extracellular pH via a neuronal activity-dependent bicarbonate shuttle. Nat. Commun. 11, 5073 (2020).","journal-title":"Nat. Commun."},{"key":"3376_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12872-5","volume":"10","author":"DM Barry","year":"2019","unstructured":"Barry, D. M. et al. Molecular determinants of nephron vascular specialization in the kidney. Nat. Commun. 10, 5705 (2019).","journal-title":"Nat. Commun."},{"key":"3376_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/srep39553","volume":"6","author":"GGJ Hazell","year":"2016","unstructured":"Hazell, G. G. J. et al. PI16 is a shear stress and inflammation-regulated inhibitor of MMP2. Sci. Rep. 6, 39553 (2016).","journal-title":"Sci. Rep."},{"key":"3376_CR29","doi-asserted-by":"publisher","first-page":"5463","DOI":"10.1073\/pnas.1913444117","volume":"117","author":"P Singhmar","year":"2020","unstructured":"Singhmar, P. et al. The fibroblast-derived protein PI16 controls neuropathic pain. Proc. Natl Acad. Sci. USA 117, 5463\u20135471 (2020).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3376_CR30","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1167\/iovs.13-13549","volume":"55","author":"A Gericke","year":"2014","unstructured":"Gericke, A. et al. Role of the M3 muscarinic acetylcholine receptor subtype in murine ophthalmic arteries after endothelial removal. Invest. Ophthalmol. Vis. Sci. 55, 625\u2013631 (2014).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"3376_CR31","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1161\/ATVBAHA.122.318820","volume":"43","author":"J-J Li","year":"2023","unstructured":"Li, J.-J. et al. Endothelial KCa3.1 and KCa2.3 mediate S1P (sphingosine-1-phosphate)\u2013dependent vasodilation and blood pressure homeostasis. Arterioscler. Thromb. Vasc. Biol. 43, 726\u2013738 (2023).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"3376_CR32","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1007\/s00424-007-0212-8","volume":"454","author":"S Reitsma","year":"2007","unstructured":"Reitsma, S., Slaaf, D. W., Vink, H., van Zandvoort, M. A. M. J. & oude Egbrink, M. G. A. The endothelial glycocalyx: composition, functions, and visualization. Pflug. Arch. 454, 345\u2013359 (2007).","journal-title":"Pflug. Arch."},{"key":"3376_CR33","doi-asserted-by":"publisher","first-page":"2660","DOI":"10.1182\/blood.V90.7.2660","volume":"90","author":"G Wu","year":"1997","unstructured":"Wu, G. et al. Human endothelial cells in culture and in vivo express on their surface all four components of the glycoprotein Ib\/IX\/V complex. Blood 90, 2660\u20132669 (1997).","journal-title":"Blood"},{"key":"3376_CR34","doi-asserted-by":"publisher","first-page":"6351","DOI":"10.3390\/ijms22126351","volume":"22","author":"GA Kelly-Robinson","year":"2021","unstructured":"Kelly-Robinson, G. A. et al. The Serpin superfamily and their role in the regulation and dysfunction of serine protease activity in COPD and other chronic lung diseases. Int. J. Mol. Sci. 22, 6351 (2021).","journal-title":"Int. J. Mol. Sci."},{"key":"3376_CR35","doi-asserted-by":"publisher","first-page":"17174","DOI":"10.1038\/s41598-023-44018-5","volume":"13","author":"Z Szeles","year":"2023","unstructured":"Szeles, Z., Pethe\u0151, G. L., Szikora, B., Kacskovics, I. & Geiszt, M. A novel monoclonal antibody reveals the enrichment of NADPH oxidase 5 in human splenic endothelial cells. Sci. Rep. 13, 17174 (2023).","journal-title":"Sci. Rep."},{"key":"3376_CR36","doi-asserted-by":"publisher","first-page":"600616","DOI":"10.3389\/fmedt.2020.600616","volume":"2","author":"AT Salminen","year":"2020","unstructured":"Salminen, A. T. et al. In vitro studies of transendothelial migration for biological and drug discovery. Front. Med. Technol. 2, 600616 (2020).","journal-title":"Front. Med. Technol."},{"key":"3376_CR37","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1001\/jamaneurol.2015.1424","volume":"72","author":"JH Lee","year":"2015","unstructured":"Lee, J. H. et al. Genetic modifiers of age at onset in carriers of the G206A mutation in PSEN1 with familial Alzheimer disease among Caribbean Hispanics. JAMA Neurol. 72, 1043\u20131051 (2015).","journal-title":"JAMA Neurol."},{"key":"3376_CR38","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1016\/j.ajpath.2011.11.022","volume":"180","author":"ARH Ahmed","year":"2012","unstructured":"Ahmed, A. R. H., Griffiths, A. B., Tilby, M. T., Westley, B. R. & May, F. E. B. TFF3 is a normal breast epithelial protein and is associated with differentiated phenotype in early breast cancer but predisposes to invasion and metastasis in advanced disease. Am. J. Pathol. 180, 904\u2013916 (2012).","journal-title":"Am. J. Pathol."},{"key":"3376_CR39","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1038\/s41556-022-00866-3","volume":"24","author":"Y Abe","year":"2022","unstructured":"Abe, Y. et al. A single-cell atlas of non-haematopoietic cells in human lymph nodes and lymphoma reveals a landscape of stromal remodelling. Nat. Cell Biol. 24, 565\u2013578 (2022).","journal-title":"Nat. Cell Biol."},{"key":"3376_CR40","doi-asserted-by":"publisher","first-page":"16487","DOI":"10.1038\/s41598-022-19885-z","volume":"12","author":"BS Steiniger","year":"2022","unstructured":"Steiniger, B. S., Pfeffer, H., Gaffling, S. & Lobachev, O. The human splenic microcirculation is entirely open as shown by 3D models in virtual reality. Sci. Rep. 12, 16487 (2022).","journal-title":"Sci. Rep."},{"key":"3376_CR41","doi-asserted-by":"publisher","first-page":"4496","DOI":"10.4049\/jimmunol.1103086","volume":"188","author":"JG Ogembo","year":"2012","unstructured":"Ogembo, J. G. et al. SIRP\u03b1 and FHOD1 are unique markers of littoral cells, a recently evolved major cell population of red pulp of human spleen. J. Immunol. 188, 4496 (2012).","journal-title":"J. Immunol."},{"key":"3376_CR42","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1182\/bloodadvances.2017015073","volume":"2","author":"J Qiu","year":"2018","unstructured":"Qiu, J. et al. The characteristics of vessel lining cells in normal spleens and their role in the pathobiology of myelofibrosis. Blood Adv. 2, 1130\u20131145 (2018).","journal-title":"Blood Adv."},{"key":"3376_CR43","doi-asserted-by":"publisher","first-page":"2247","DOI":"10.1038\/s41596-020-0336-2","volume":"15","author":"B Van de Sande","year":"2020","unstructured":"Van de Sande, B. et al. A scalable SCENIC workflow for single-cell gene regulatory network analysis. Nat. Protoc. 15, 2247\u20132276 (2020).","journal-title":"Nat. Protoc."},{"key":"3376_CR44","first-page":"1586","volume":"93","author":"K Morohashi","year":"1999","unstructured":"Morohashi, K. et al. Structural and functional abnormalities in the spleen of an mFtz-F1 gene-disrupted mouse. Blood 93, 1586\u20131594 (1999).","journal-title":"Blood"},{"key":"3376_CR45","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1172\/JCI73186","volume":"124","author":"D Zangen","year":"2014","unstructured":"Zangen, D. et al. Testicular differentiation factor SF-1 is required for human spleen development. J. Clin. Invest. 124, 2071\u20132075 (2014).","journal-title":"J. Clin. Invest."},{"key":"3376_CR46","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.3390\/ijms21041429","volume":"21","author":"N Emura","year":"2020","unstructured":"Emura, N., Wang, C.-M., Yang, W. H. & Yang, W.-H. Steroidogenic factor 1 (NR5A1) activates ATF3 transcriptional activity. Int. J. Mol. Sci. 21, 1429 (2020).","journal-title":"Int. J. Mol. Sci."},{"key":"3376_CR47","doi-asserted-by":"publisher","first-page":"603507","DOI":"10.3389\/fimmu.2020.603507","volume":"11","author":"MA Vega","year":"2020","unstructured":"Vega, M. A. et al. MAFB and MAF transcription factors as macrophage checkpoints for COVID-19 severity. Front. Immunol. 11, 603507 (2020).","journal-title":"Front. Immunol."},{"key":"3376_CR48","doi-asserted-by":"publisher","first-page":"a036723","DOI":"10.1101\/cshperspect.a036723","volume":"12","author":"B Dye","year":"2020","unstructured":"Dye, B. & Lincoln, J. The endocardium and heart valves. Cold Spring Harb. Perspect. Biol. 12, a036723 (2020).","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"3376_CR49","doi-asserted-by":"publisher","first-page":"eabo1984","DOI":"10.1126\/science.abo1984","volume":"377","author":"D Reichart","year":"2022","unstructured":"Reichart, D. et al. Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies. Science 377, eabo1984 (2022).","journal-title":"Science"},{"key":"3376_CR50","doi-asserted-by":"publisher","first-page":"4006","DOI":"10.1073\/pnas.1019025108","volume":"108","author":"IP Moskowitz","year":"2011","unstructured":"Moskowitz, I. P. et al. Transcription factor genes Smad4 and Gata4 cooperatively regulate cardiac valve development. Proc. Natl Acad. Sci. USA 108, 4006\u20134011 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3376_CR51","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1203\/PDR.0b013e3181ed17e4","volume":"68","author":"M Maitra","year":"2010","unstructured":"Maitra, M., Koenig, S. N., Srivastava, D. & Garg, V. Identification of GATA6 sequence variants in patients with congenital heart defects. Pediatr. Res. 68, 281\u2013285 (2010).","journal-title":"Pediatr. Res."},{"key":"3376_CR52","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1038\/s41586-023-06311-1","volume":"619","author":"K Kanemaru","year":"2023","unstructured":"Kanemaru, K. et al. Spatially resolved multiomics of human cardiac niches. Nature 619, 801\u2013810 (2023).","journal-title":"Nature"},{"key":"3376_CR53","doi-asserted-by":"crossref","unstructured":"Ataga, K. I. et al. Crizanlizumab for the prevention of pain crises in sickle cell disease. N. Engl. J. Med. 376, 429\u2013439 (2017).","DOI":"10.1056\/NEJMoa1611770"},{"key":"3376_CR54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1152\/physiolgenomics.00062.2017","volume":"50","author":"HC Saternos","year":"2018","unstructured":"Saternos, H. C. et al. Distribution and function of the muscarinic receptor subtypes in the cardiovascular system. Physiol. Genomics 50, 1\u20139 (2018).","journal-title":"Physiol. Genomics"},{"key":"3376_CR55","doi-asserted-by":"publisher","first-page":"588\u2013591","DOI":"10.1161\/HYPERTENSIONAHA.118.11494","volume":"72","author":"A Cowley Jr.","year":"2018","unstructured":"Cowley, A. Jr. Chrm3 gene and M3 muscarinic receptors contribute to salt-sensitive hypertension: but now a physiological puzzle. Hypertension 72, 588\u2013591 (2018).","journal-title":"Hypertension"},{"key":"3376_CR56","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/j.cjca.2019.02.003","volume":"35","author":"R Alves-Lopes","year":"2019","unstructured":"Alves-Lopes, R., Neves, K. B. & Touyz, R. M. Muscarinic receptor type-3 in hypertension and cholinergic-adrenergic crosstalk: genetic insights and potential for new antihypertensive targets. Can. J. Cardiol. 35, 555\u2013557 (2019).","journal-title":"Can. J. Cardiol."},{"key":"3376_CR57","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1001\/jama.1962.03050300059020a","volume":"181","author":"RC Laughlin","year":"1962","unstructured":"Laughlin, R. C. & Carey, T. F. Cataracts in patients treated with triparanol. JAMA 181, 339\u2013340 (1962).","journal-title":"JAMA"},{"key":"3376_CR58","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.acthis.2009.07.004","volume":"113","author":"E Cano-Europa","year":"2011","unstructured":"Cano-Europa, E., Blas-Valdivia, V., Franco-Colin, M., Gallardo-Casas, C. A. & Ortiz-Butr\u00f3n, R. Methimazole-induced hypothyroidism causes cellular damage in the spleen, heart, liver, lung and kidney. Acta Histochem. 113, 1\u20135 (2011).","journal-title":"Acta Histochem."},{"key":"3376_CR59","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/0034-5288(93)90134-2","volume":"54","author":"ME Peterson","year":"1993","unstructured":"Peterson, M. E. & Aucoin, D. P. Comparison of the disposition of carbimazole and methimazole in clinically normal cats. Res. Vet. Sci. 54, 351\u2013355 (1993).","journal-title":"Res. Vet. Sci."},{"key":"3376_CR60","doi-asserted-by":"publisher","first-page":"282","DOI":"10.3803\/EnM.2022.1643","volume":"38","author":"DH Kang","year":"2023","unstructured":"Kang, D. H., Song, M.-K., Ju, S.-H., Lee, S.-I. & Kang, Y. E. Propylthiouracil-induced antineutrophil cytoplasmic antibody-positive vasculitis and agranulocytosis: a rare case with life-threatening multiple systemic manifestations. Endocrinol. Metab. (Seoul) 38, 282\u2013284 (2023).","journal-title":"Endocrinol. Metab. (Seoul)"},{"key":"3376_CR61","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1161\/CIRCULATIONAHA.114.013721","volume":"131","author":"G Coppiello","year":"2015","unstructured":"Coppiello, G. et al. Meox2\/Tcf15 heterodimers program the heart capillary endothelium for cardiac fatty acid uptake. Circulation 131, 815\u2013826 (2015).","journal-title":"Circulation"},{"key":"3376_CR62","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.molmet.2015.04.004","volume":"4","author":"DV Chartoumpekis","year":"2015","unstructured":"Chartoumpekis, D. V. et al. Notch intracellular domain overexpression in adipocytes confers lipodystrophy in mice. Mol. Metab. 4, 543\u2013550 (2015).","journal-title":"Mol. Metab."},{"key":"3376_CR63","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1189\/jlb.1008621","volume":"85","author":"H Yang","year":"2009","unstructured":"Yang, H. et al. Axin expression in thymic stromal cells contributes to an age-related increase in thymic adiposity and is associated with reduced thymopoiesis independently of ghrelin signaling. J. Leukoc. Biol. 85, 928\u2013938 (2009).","journal-title":"J. Leukoc. Biol."},{"key":"3376_CR64","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1038\/s41586-020-2822-7","volume":"586","author":"A Gillich","year":"2020","unstructured":"Gillich, A. et al. Capillary cell-type specialization in the alveolus. Nature 586, 785\u2013789 (2020).","journal-title":"Nature"},{"key":"3376_CR65","doi-asserted-by":"publisher","first-page":"1800475","DOI":"10.1183\/13993003.00475-2018","volume":"52","author":"NT Vozoris","year":"2018","unstructured":"Vozoris, N. T. et al. Serotonergic antidepressant use and morbidity and mortality among older adults with COPD. Eur. Respir. J. 52, 1800475 (2018).","journal-title":"Eur. Respir. J."},{"key":"3376_CR66","doi-asserted-by":"publisher","first-page":"2560","DOI":"10.1038\/s41467-023-38177-2","volume":"14","author":"F Bian","year":"2023","unstructured":"Bian, F. et al. Lung endothelial cells regulate pulmonary fibrosis through FOXF1\/R-Ras signaling. Nat. Commun. 14, 2560 (2023).","journal-title":"Nat. Commun."},{"key":"3376_CR67","doi-asserted-by":"publisher","first-page":"100233","DOI":"10.1016\/j.labinv.2023.100233","volume":"103","author":"GG Edel","year":"2023","unstructured":"Edel, G. G. et al. Clinical relevance of rapid FOXF1-targeted sequencing in patients suspected of alveolar capillary dysplasia with misalignment of pulmonary veins. Lab. Invest. 103, 100233 (2023).","journal-title":"Lab. Invest."},{"key":"3376_CR68","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.ccell.2019.12.001","volume":"37","author":"J Goveia","year":"2020","unstructured":"Goveia, J. et al. An integrated gene expression landscape profiling approach to identify lung tumor endothelial cell heterogeneity and angiogenic candidates. Cancer Cell 37, 21\u201336 (2020).","journal-title":"Cancer Cell"},{"key":"3376_CR69","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1161\/CIRCRESAHA.118.313645","volume":"124","author":"D Schneller","year":"2019","unstructured":"Schneller, D. et al. Cytokine-like 1 is a novel proangiogenic factor secreted by and mediating functions of endothelial progenitor cells. Circ. Res. 124, 243\u2013255 (2019).","journal-title":"Circ. Res."},{"key":"3376_CR70","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1681\/ASN.2021030294","volume":"33","author":"NC Finch","year":"2022","unstructured":"Finch, N. C. et al. Reduced glomerular filtration in diabetes is attributable to loss of density and increased resistance of glomerular endothelial cell fenestrations. J. Am. Soc. Nephrol. 33, 1120\u20131136 (2022).","journal-title":"J. Am. Soc. Nephrol."},{"key":"3376_CR71","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1038\/s41419-020-03022-7","volume":"11","author":"Q Deng","year":"2020","unstructured":"Deng, Q. et al. Increased long noncoding RNA maternally expressed gene 3 contributes to podocyte injury induced by high glucose through regulation of mitochondrial fission. Cell Death Dis. 11, 814 (2020).","journal-title":"Cell Death Dis."},{"key":"3376_CR72","first-page":"687\u2013699","volume":"37","author":"A De Mar\u00e9","year":"2022","unstructured":"De Mar\u00e9, A., Opdebeeck, B., Neven, E., D\u2019Haese, P. C. & Verhulst, A. Sclerostin protects against vascular calcification development in mice. J. Bone Miner. Res. 37, 687\u2013699 (2022).","journal-title":"J. Bone Miner. Res."},{"key":"3376_CR73","doi-asserted-by":"publisher","first-page":"e80","DOI":"10.5858\/2003-127-e80-GCIH","volume":"127","author":"JR Henegar","year":"2003","unstructured":"Henegar, J. R., Coleman, J. P., Cespedes, J. & Hughson, M. D. Glomerular calcification in hypercalcemic nephropathy. Arch. Pathol. Lab. Med. 127, e80\u2013e85 (2003).","journal-title":"Arch. Pathol. Lab. Med."},{"key":"3376_CR74","doi-asserted-by":"publisher","first-page":"2150","DOI":"10.1016\/j.apsb.2022.01.012","volume":"12","author":"S Yu","year":"2022","unstructured":"Yu, S. et al. Drug discovery of sclerostin inhibitors. Acta Pharm. Sin. B 12, 2150\u20132170 (2022).","journal-title":"Acta Pharm. Sin. B"},{"key":"3376_CR75","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1038\/s41419-022-04803-y","volume":"13","author":"C Song","year":"2022","unstructured":"Song, C. et al. IGFBP5 promotes diabetic kidney disease progression by enhancing PFKFB3-mediated endothelial glycolysis. Cell Death Dis. 13, 340 (2022).","journal-title":"Cell Death Dis."},{"key":"3376_CR76","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-49236-7","volume":"15","author":"A Brazovskaja","year":"2024","unstructured":"Brazovskaja, A. et al. Cell atlas of the regenerating human liver after portal vein embolization. Nat. Commun. 15, 5827 (2024).","journal-title":"Nat. Commun."},{"key":"3376_CR77","doi-asserted-by":"publisher","first-page":"987481","DOI":"10.3389\/fonc.2022.987481","volume":"12","author":"L-T Wang","year":"2022","unstructured":"Wang, L.-T. et al. Ficolin-2: a potential immune-related therapeutic target with low expression in liver cancer. Front. Oncol. 12, 987481 (2022).","journal-title":"Front. Oncol."},{"key":"3376_CR78","doi-asserted-by":"publisher","first-page":"148","DOI":"10.3389\/fped.2014.00148","volume":"2","author":"MH Beltrame","year":"2015","unstructured":"Beltrame, M. H., Catarino, S. J., Goeldner, I., Boldt, A. B. W. & de Messias-Reason, I. J. The lectin pathway of complement and rheumatic heart disease. Front. Pediatr. 2, 148 (2015).","journal-title":"Front. Pediatr."},{"key":"3376_CR79","doi-asserted-by":"publisher","first-page":"2323","DOI":"10.3389\/fmicb.2017.02323","volume":"8","author":"SA Iacob","year":"2017","unstructured":"Iacob, S. A. & Iacob, D. G. Ibalizumab targeting CD4 receptors, an emerging molecule in HIV therapy. Front. Microbiol. 8, 2323 (2017).","journal-title":"Front. Microbiol."},{"key":"3376_CR80","doi-asserted-by":"publisher","first-page":"21416","DOI":"10.1074\/jbc.M110.103499","volume":"285","author":"KS Kim","year":"2010","unstructured":"Kim, K. S., Park, J.-Y., Jou, I. & Park, S. M. Regulation of Weibel\u2013Palade body exocytosis by \u03b1-synuclein in endothelial cells. J. Biol. Chem. 285, 21416\u201321425 (2010).","journal-title":"J. Biol. Chem."},{"key":"3376_CR81","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1038\/s41586-021-03782-y","volume":"596","author":"CAP Wood","year":"2021","unstructured":"Wood, C. A. P. et al. Structure and mechanism of blood\u2013brain-barrier lipid transporter MFSD2A. Nature 596, 444\u2013448 (2021).","journal-title":"Nature"},{"key":"3376_CR82","doi-asserted-by":"publisher","first-page":"3742","DOI":"10.3390\/ijms22073742","volume":"22","author":"SB Al Rihani","year":"2021","unstructured":"Al Rihani, S. B. et al. Disease-induced modulation of drug transporters at the blood\u2013brain barrier level. Int. J. Mol. Sci. 22, 3742 (2021).","journal-title":"Int. J. Mol. Sci."},{"key":"3376_CR83","doi-asserted-by":"publisher","first-page":"1637","DOI":"10.1038\/jcbfm.2011.21","volume":"31","author":"N Ruderisch","year":"2011","unstructured":"Ruderisch, N., Virgintino, D., Makrides, V. & Verrey, F. Differential axial localization along the mouse brain vascular tree of luminal sodium-dependent glutamine transporters Snat1 and Snat3. J. Cereb. Blood Flow. Metab. 31, 1637\u20131647 (2011).","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"3376_CR84","doi-asserted-by":"publisher","first-page":"570922","DOI":"10.3389\/fphys.2020.00973","volume":"11","author":"R Zaragoz\u00e1","year":"2020","unstructured":"Zaragoz\u00e1, R. Transport of amino acids across the blood\u2013brain barrier. Front. Physiol. 11, 570922 (2020).","journal-title":"Front. Physiol."},{"key":"3376_CR85","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1038\/nature13324","volume":"509","author":"A Ben-Zvi","year":"2014","unstructured":"Ben-Zvi, A. et al. Mfsd2a is critical for the formation and function of the blood\u2013brain barrier. Nature 509, 507\u2013511 (2014).","journal-title":"Nature"},{"key":"3376_CR86","doi-asserted-by":"publisher","first-page":"2219","DOI":"10.1056\/NEJMoa2025845","volume":"383","author":"GL Bakris","year":"2020","unstructured":"Bakris, G. L. et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N. Engl. J. Med. 383, 2219\u20132229 (2020).","journal-title":"N. Engl. J. Med."},{"key":"3376_CR87","first-page":"236","volume":"10","author":"F Piccirillo","year":"2023","unstructured":"Piccirillo, F. et al. Effects of finerenone on cardiovascular and chronic kidney diseases: a new weapon against cardiorenal morbidity and mortality\u2014a comprehensive review. J. Cardiovasc. Dev. Dis. 10, 236 (2023).","journal-title":"J. Cardiovasc. Dev. Dis."},{"key":"3376_CR88","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1038\/cgt.2017.8","volume":"24","author":"HY Liu","year":"2017","unstructured":"Liu, H. Y. & Zhang, C. J. Identification of differentially expressed genes and their upstream regulators in colorectal cancer. Cancer Gene Ther. 24, 244\u2013250 (2017).","journal-title":"Cancer Gene Ther."},{"key":"3376_CR89","doi-asserted-by":"publisher","first-page":"1064980","DOI":"10.3389\/fgene.2022.1064980","volume":"13","author":"H-Y Fan","year":"2023","unstructured":"Fan, H.-Y. et al. Targeted next-generation sequencing for genetic variants of left ventricular mass status among community-based adults in Taiwan. Front. Genet. 13, 1064980 (2023).","journal-title":"Front. Genet."},{"key":"3376_CR90","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1681\/ASN.2011121159","volume":"23","author":"T Matsusaka","year":"2012","unstructured":"Matsusaka, T. et al. Liver angiotensinogen is the primary source of renal angiotensin II. J. Am. Soc. Nephrol. 23, 1181\u20131189 (2012).","journal-title":"J. Am. Soc. Nephrol."},{"key":"3376_CR91","doi-asserted-by":"publisher","first-page":"R123\u2013R134","DOI":"10.1530\/JOE-16-0594","volume":"234","author":"RT Scarl","year":"2017","unstructured":"Scarl, R. T., Martin Lawrence, C., Gordon, H. M. & Nunemaker, C. S. STEAP4: its emerging role in metabolism and homeostasis of cellular iron and copper. J. Endocrinol. 234, R123\u2013R134 (2017).","journal-title":"J. Endocrinol."},{"key":"3376_CR92","first-page":"1138","volume":"14","author":"R Kane","year":"2008","unstructured":"Kane, R., Godson, C. & O\u2019Brien, C. Chordin-like 1, a bone morphogenetic protein-4 antagonist, is upregulated by hypoxia in human retinal pericytes and plays a role in regulating angiogenesis. Mol. Vis. 14, 1138\u20131148 (2008).","journal-title":"Mol. Vis."},{"key":"3376_CR93","doi-asserted-by":"publisher","first-page":"L872","DOI":"10.1152\/ajplung.00254.2018","volume":"316","author":"J Park","year":"2019","unstructured":"Park, J. et al. The Tcf21 lineage constitutes the lung lipofibroblast population. Am. J. Physiol. Lung Cell. Mol. Physiol. 316, L872\u2013L885 (2019).","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"3376_CR94","doi-asserted-by":"publisher","first-page":"2825","DOI":"10.3390\/ijms25052825","volume":"25","author":"MM Smith","year":"2024","unstructured":"Smith, M. M. & Melrose, J. Lumican, a multifunctional cell instructive biomarker proteoglycan has novel roles as a marker of the hypercoagulative state of long COVID disease. Int. J. Mol. Sci. 25, 2825 (2024).","journal-title":"Int. J. Mol. Sci."},{"key":"3376_CR95","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1016\/j.neuron.2017.10.025","volume":"96","author":"J Mazzoni","year":"2017","unstructured":"Mazzoni, J. et al. The Wnt inhibitor Apcdd1 coordinates vascular remodeling and barrier maturation of retinal blood vessels. Neuron 96, 1055\u20131069 (2017).","journal-title":"Neuron"},{"key":"3376_CR96","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/s42003-022-03029-0","volume":"5","author":"T Fan","year":"2022","unstructured":"Fan, T. et al. Phosphodiesterase 4D promotes angiotensin II-induced hypertension in mice via smooth muscle cell contraction. Commun. Biol. 5, 81 (2022).","journal-title":"Commun. Biol."},{"key":"3376_CR97","doi-asserted-by":"publisher","first-page":"2431","DOI":"10.1161\/ATVBAHA.121.316219","volume":"41","author":"Y Cai","year":"2021","unstructured":"Cai, Y. et al. Salt-inducible kinase 3 promotes vascular smooth muscle cell proliferation and arterial restenosis by regulating AKT and PKA-CREB signaling. Arterioscler. Thromb. Vasc. Biol. 41, 2431\u20132451 (2021).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"3376_CR98","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1038\/s41586-022-04918-4","volume":"607","author":"L Garcia-Alonso","year":"2022","unstructured":"Garcia-Alonso, L. et al. Single-cell roadmap of human gonadal development. Nature 607, 540\u2013547 (2022).","journal-title":"Nature"},{"key":"3376_CR99","doi-asserted-by":"publisher","first-page":"102254","DOI":"10.1016\/j.ceb.2023.102254","volume":"85","author":"H Cuervo","year":"2023","unstructured":"Cuervo, H., M\u00fchleder, S., Garc\u00eda-G\u00f3nzalez, I. & Benedito, R. Notch-mediated cellular interactions between vascular cells. Curr. Opin. Cell Biol. 85, 102254 (2023).","journal-title":"Curr. Opin. Cell Biol."},{"key":"3376_CR100","doi-asserted-by":"publisher","first-page":"3845","DOI":"10.1002\/jcp.30838","volume":"237","author":"L Louvet","year":"2022","unstructured":"Louvet, L. et al. Vasorin plays a critical role in vascular smooth muscle cells and arterial functions. J. Cell. Physiol. 237, 3845\u20133859 (2022).","journal-title":"J. Cell. Physiol."},{"key":"3376_CR101","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1161\/01.HYP.0000018588.56950.7A","volume":"39","author":"B Li","year":"2002","unstructured":"Li, B. et al. KDR (VEGF receptor 2) is the major mediator for the hypotensive effect of VEGF. Hypertension 39, 1095\u20131100 (2002).","journal-title":"Hypertension"},{"key":"3376_CR102","doi-asserted-by":"publisher","first-page":"599281","DOI":"10.3389\/fcell.2020.599281","volume":"8","author":"X Wang","year":"2020","unstructured":"Wang, X., Bove, A. M., Simone, G. & Ma, B. Molecular bases of VEGFR-2-mediated physiological function and pathological role. Front. Cell. Dev. Biol. 8, 599281 (2020).","journal-title":"Front. Cell. Dev. Biol."},{"key":"3376_CR103","doi-asserted-by":"publisher","first-page":"C424\u2013C433","DOI":"10.1152\/ajpcell.00405.2018","volume":"316","author":"M Mahmoud","year":"2019","unstructured":"Mahmoud, M. et al. Smooth muscle cell-specific knockout of neuropilin-1 impairs postnatal lung development and pathological vascular smooth muscle cell accumulation. Am. J. Physiol. Cell Physiol. 316, C424\u2013C433 (2019).","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"3376_CR104","doi-asserted-by":"publisher","first-page":"869","DOI":"10.3390\/biom12070869","volume":"12","author":"Q Deng","year":"2022","unstructured":"Deng, Q. & Chen, J. Potential therapeutic effect of all-trans retinoic acid on atherosclerosis. Biomolecules 12, 869 (2022).","journal-title":"Biomolecules"},{"key":"3376_CR105","doi-asserted-by":"publisher","first-page":"e84969","DOI":"10.1371\/journal.pone.0084969","volume":"9","author":"L Campagnolo","year":"2014","unstructured":"Campagnolo, L. et al. Sortilin expression is essential for pro-nerve growth factor-induced apoptosis of rat vascular smooth muscle cells. PLoS ONE 9, e84969 (2014).","journal-title":"PLoS ONE"},{"key":"3376_CR106","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.mce.2017.09.022","volume":"465","author":"I Simitsidellis","year":"2018","unstructured":"Simitsidellis, I., Saunders, P. T. K. & Gibson, D. A. Androgens and endometrium: new insights and new targets. Mol. Cell. Endocrinol. 465, 48\u201360 (2018).","journal-title":"Mol. Cell. Endocrinol."},{"key":"3376_CR107","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s12974-024-03068-w","volume":"21","author":"D Liu","year":"2024","unstructured":"Liu, D. et al. Wnt5a\/\u03b2-catenin-mediated epithelial-mesenchymal transition: a key driver of subretinal fibrosis in neovascular age-related macular degeneration. J. Neuroinflammation 21, 75 (2024).","journal-title":"J. Neuroinflammation"},{"key":"3376_CR108","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s41592-021-01336-8","volume":"19","author":"MD Luecken","year":"2022","unstructured":"Luecken, M. D. et al. Benchmarking atlas-level data integration in single-cell genomics. Nat. Methods 19, 41\u201350 (2022).","journal-title":"Nat. Methods"},{"key":"3376_CR109","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1161\/01.RES.0000255691.76142.4a","volume":"100","author":"WC Aird","year":"2007","unstructured":"Aird, W. C. Phenotypic heterogeneity of the endothelium. Circ. Res. 100, 158\u2013173 (2007).","journal-title":"Circ. Res."},{"key":"3376_CR110","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37126-3","volume":"14","author":"HCT Nguyen","year":"2023","unstructured":"Nguyen, H. C. T., Baik, B., Yoon, S., Park, T. & Nam, D. Benchmarking integration of single-cell differential expression. Nat. Commun. 14, 1570 (2023).","journal-title":"Nat. Commun."},{"key":"3376_CR111","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0844-5","volume":"16","author":"G Finak","year":"2015","unstructured":"Finak, G. et al. MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data. Genome Biol. 16, 278 (2015).","journal-title":"Genome Biol."},{"key":"3376_CR112","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1186\/s13059-020-02048-6","volume":"21","author":"E Denisenko","year":"2020","unstructured":"Denisenko, E. et al. Systematic assessment of tissue dissociation and storage biases in single-cell and single-nucleus RNA-seq workflows. Genome Biol. 21, 130 (2020).","journal-title":"Genome Biol."},{"key":"3376_CR113","doi-asserted-by":"publisher","first-page":"849","DOI":"10.2147\/JPR.S278285","volume":"14","author":"NR Karki","year":"2021","unstructured":"Karki, N. R. & Kutlar, A. P-selectin blockade in the treatment of painful vaso-occlusive crises in sickle cell disease: a spotlight on crizanlizumab. J. Pain. Res. 14, 849\u2013856 (2021).","journal-title":"J. Pain. Res."},{"key":"3376_CR114","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cels.2018.11.005","volume":"8","author":"SL Wolock","year":"2019","unstructured":"Wolock, S. L., Lopez, R. & Klein, A. M. Scrublet: computational identification of cell doublets in single-cell transcriptomic data. Cell Syst. 8, 281\u2013291 (2019).","journal-title":"Cell Syst."},{"key":"3376_CR115","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13059-017-1382-0","volume":"19","author":"FA Wolf","year":"2018","unstructured":"Wolf, F. A., Angerer, P. & Theis, F. J. SCANPY: large-scale single-cell gene expression data analysis. Genome Biol. 19, 15 (2018).","journal-title":"Genome Biol."},{"key":"3376_CR116","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1038\/s41592-018-0229-2","volume":"15","author":"R Lopez","year":"2018","unstructured":"Lopez, R., Regier, J., Cole, M. B., Jordan, M. I. & Yosef, N. Deep generative modeling for single-cell transcriptomics. Nat. Methods 15, 1053\u20131058 (2018).","journal-title":"Nat. Methods"},{"key":"3376_CR117","doi-asserted-by":"publisher","first-page":"btac746","DOI":"10.1093\/bioinformatics\/btac746","volume":"39","author":"L Faure","year":"2022","unstructured":"Faure, L., Soldatov, R., Kharchenko, P. V. & Adameyko, I. scFates: a scalable Python package for advanced pseudotime and bifurcation analysis from single-cell data. Bioinformatics 39, btac746 (2022).","journal-title":"Bioinformatics"},{"key":"3376_CR118","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","volume":"16","author":"I Korsunsky","year":"2019","unstructured":"Korsunsky, I. et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat. Methods 16, 1289\u20131296 (2019).","journal-title":"Nat. Methods"},{"key":"3376_CR119","unstructured":"Troul\u00e9, K. et al. CellPhoneDB v5: inferring cell\u2013cell communication from single-cell multiomics data. Preprint at https:\/\/arxiv.org\/abs\/2311.04567 (2023)."},{"key":"3376_CR120","doi-asserted-by":"publisher","first-page":"eabl5197","DOI":"10.1126\/science.abl5197","volume":"376","author":"C Dom\u00ednguez Conde","year":"2022","unstructured":"Dom\u00ednguez Conde, C. et al. Cross-tissue immune cell analysis reveals tissue-specific features in humans. Science 376, eabl5197 (2022).","journal-title":"Science"},{"key":"3376_CR121","doi-asserted-by":"publisher","first-page":"1698","DOI":"10.1038\/s41588-021-00972-2","volume":"53","author":"L Garcia-Alonso","year":"2021","unstructured":"Garcia-Alonso, L. et al. Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro. Nat. Genet. 53, 1698\u20131711 (2021).","journal-title":"Nat. Genet."},{"key":"3376_CR122","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/s41587-021-01139-4","volume":"40","author":"V Kleshchevnikov","year":"2022","unstructured":"Kleshchevnikov, V. et al. Cell2location maps fine-grained cell types in spatial transcriptomics. Nat. Biotechnol. 40, 661\u2013671 (2022).","journal-title":"Nat. Biotechnol."},{"key":"3376_CR123","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/s41556-023-01316-4","volume":"26","author":"C Bravo Gonz\u00e1lez-Blas","year":"2024","unstructured":"Bravo Gonz\u00e1lez-Blas, C. et al. Single-cell spatial multi-omics and deep learning dissect enhancer-driven gene regulatory networks in liver zonation. Nat. Cell. Biol. 26, 153\u2013167 (2024).","journal-title":"Nat. Cell. Biol."},{"key":"3376_CR124","doi-asserted-by":"publisher","first-page":"D766","DOI":"10.1093\/nar\/gky955","volume":"47","author":"A Frankish","year":"2019","unstructured":"Frankish, A. et al. GENCODE reference annotation for the human and mouse genomes. Nucleic Acids Res. 47, D766\u2013D773 (2019).","journal-title":"Nucleic Acids Res."},{"key":"3376_CR125","doi-asserted-by":"crossref","first-page":"D682","DOI":"10.1093\/nar\/gkz1138","volume":"48","author":"AD Yates","year":"2020","unstructured":"Yates, A. D. et al. Ensembl 2020. Nucleic Acids Res. 48, D682\u2013D688 (2020).","journal-title":"Nucleic Acids Res."},{"key":"3376_CR126","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1093\/bioinformatics\/btr011","volume":"27","author":"G Mar\u00e7ais","year":"2011","unstructured":"Mar\u00e7ais, G. & Kingsford, C. A fast, lock-free approach for efficient parallel counting of occurrences of k-mers. Bioinformatics 27, 764\u2013770 (2011).","journal-title":"Bioinformatics"},{"key":"3376_CR127","doi-asserted-by":"publisher","first-page":"e74","DOI":"10.1093\/nar\/gkn301","volume":"36","author":"JD Gans","year":"2008","unstructured":"Gans, J. D. & Wolinsky, M. Improved assay-dependent searching of nucleic acid sequence databases. Nucleic Acids Res. 36, e74 (2008).","journal-title":"Nucleic Acids Res."},{"key":"3376_CR128","doi-asserted-by":"publisher","first-page":"D213","DOI":"10.1093\/nar\/gkx997","volume":"46","author":"JM Rodriguez","year":"2018","unstructured":"Rodriguez, J. M. et al. APPRIS 2017: principal isoforms for multiple gene sets. Nucleic Acids Res. 46, D213\u2013D217 (2018).","journal-title":"Nucleic Acids Res."},{"key":"3376_CR129","doi-asserted-by":"publisher","first-page":"3021","DOI":"10.21105\/joss.03021","volume":"6","author":"ML Waskom","year":"2021","unstructured":"Waskom, M. L. seaborn: statistical data visualization. J. Open Source Softw. 6, 3021 (2021).","journal-title":"J. Open Source Softw."},{"key":"3376_CR130","first-page":"2825","volume":"12","author":"F Pedregosa","year":"2011","unstructured":"Pedregosa, F. et al. Scikit-learn: machine learning in Python. J. Mach. Learn. Res. 12, 2825\u20132830 (2011).","journal-title":"J. Mach. Learn. Res."}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41591-024-03376-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-024-03376-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-024-03376-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T09:55:36Z","timestamp":1736330136000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-024-03376-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,20]]},"references-count":130,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["3376"],"URL":"https:\/\/doi.org\/10.1038\/s41591-024-03376-x","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,20]]},"assertion":[{"value":"16 November 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 October 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 November 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"In the past 3 years, S.A.T. has consulted for or been a member of scientific advisory boards (SABs) at Qiagen, OMass Therapeutics, Xaira Therapeutics and ForeSite Labs, and a non-executive director of 10x Genomics. She is a co-founder and equity holder of TransitionBio and Ensocell, and a part-time employee at GSK. R.E. is a co-founder and equity holder in Ensocell. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}