{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:54:10Z","timestamp":1793296450914,"version":"4.5.0"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T00:00:00Z","timestamp":1596153600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T00:00:00Z","timestamp":1596153600000},"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 Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Upon severe head injury (HI), blood vessels of the meninges and brain parenchyma are inevitably damaged. While limited vascular regeneration of the injured brain has been studied extensively, our understanding of meningeal vascular regeneration following head injury is quite limited. Here, we identify key pathways governing meningeal vascular regeneration following HI. Rapid and complete vascular regeneration in the meninges is predominantly driven by VEGFR2 signaling. Substantial increase of VEGFR2 is observed in both human patients and mouse models of HI, and endothelial cell-specific deletion of <jats:italic>Vegfr2<\/jats:italic> in the latter inhibits meningeal vascular regeneration. We further identify the facilitating, stabilizing and arresting roles of Tie2, PDGFR\u03b2 and Dll4 signaling, respectively, in meningeal vascular regeneration. Prolonged inhibition of this angiogenic process following HI compromises immunological and stromal integrity of the injured meninges. These findings establish a molecular framework for meningeal vascular regeneration after HI, and may guide development of wound healing therapeutics.<\/jats:p>","DOI":"10.1038\/s41467-020-17545-2","type":"journal-article","created":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T10:05:51Z","timestamp":1596189951000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["VEGFR2 signaling drives meningeal vascular regeneration upon head injury"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3636-0492","authenticated-orcid":false,"given":"Bong Ihn","family":"Koh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyuek Jong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pil Ae","family":"Kwak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung Jin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju-Hee","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung-Seok","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1231-1485","authenticated-orcid":false,"given":"Gou Young","family":"Koh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9244-815X","authenticated-orcid":false,"given":"Injune","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,31]]},"reference":[{"key":"17545_CR1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nrneurol.2013.22","volume":"9","author":"B Roozenbeek","year":"2013","unstructured":"Roozenbeek, B., Maas, A. I. R. & Menon, D. K. Changing patterns in the epidemiology of traumatic brain injury. Nat. Rev. Neurol. 9, 231\u2013236 (2013).","journal-title":"Nat. Rev. Neurol."},{"key":"17545_CR2","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1017\/cjn.2016.290","volume":"43","author":"R Nguyen","year":"2016","unstructured":"Nguyen, R. et al. The international incidence of traumatic brain injury: a systematic review and meta-analysis. Can. J. Neurol. Sci. 43, 774\u2013785 (2016).","journal-title":"Can. J. Neurol. Sci."},{"key":"17545_CR3","doi-asserted-by":"crossref","first-page":"16084","DOI":"10.1038\/nrdp.2016.84","volume":"2","author":"K Blennow","year":"2016","unstructured":"Blennow, K. et al. Traumatic brain injuries. Nat. Rev. Dis. Prim. 2, 16084 (2016).","journal-title":"Nat. Rev. Dis. Prim."},{"key":"17545_CR4","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/nrneurol.2013.38","volume":"9","author":"M Rusnak","year":"2013","unstructured":"Rusnak, M. Traumatic brain injury: giving voice to a silent epidemic. Nat. Rev. Neurol. 9, 186\u2013187 (2013).","journal-title":"Nat. Rev. Neurol."},{"key":"17545_CR5","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/nrneurol.2013.36","volume":"9","author":"ST Dekosky","year":"2013","unstructured":"Dekosky, S. T., Blennow, K., Ikonomovic, M. D. & Gandy, S. Acute and chronic traumatic encephalopathies: pathogenesis and biomarkers. Nat. Rev. Neurol. 9, 192\u2013200 (2013).","journal-title":"Nat. Rev. Neurol."},{"key":"17545_CR6","first-page":"92","volume":"1","author":"I Decimo","year":"2012","unstructured":"Decimo, I., Fumagalli, G., Berton, V., Krampera, M. & Bifari, F. Meninges: from protective membrane to stem cell niche. Am. J. Stem Cells 1, 92\u2013105 (2012).","journal-title":"Am. J. Stem Cells"},{"key":"17545_CR7","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s00401-018-1809-z","volume":"135","author":"RO Weller","year":"2018","unstructured":"Weller, R. O., Sharp, M. M., Christodoulides, M., Carare, R. O. & M\u00f8llg\u00e5rd, K. The meninges as barriers and facilitators for the movement of fluid, cells and pathogens related to the rodent and human CNS. Acta Neuropathol. 135, 363\u2013385 (2018).","journal-title":"Acta Neuropathol."},{"key":"17545_CR8","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/j.acthis.2018.09.009","volume":"120","author":"B Mecheri","year":"2018","unstructured":"Mecheri, B., Paris, F. & L\u00fcbbert, H. Histological investigations on the dura mater vascular system of mice. Acta Histochem. 120, 846\u2013857 (2018).","journal-title":"Acta Histochem."},{"key":"17545_CR9","doi-asserted-by":"crossref","first-page":"eaav0492","DOI":"10.1126\/sciimmunol.aav0492","volume":"4","author":"P Mastorakos","year":"2019","unstructured":"Mastorakos, P. & McGavern, D. The anatomy and immunology of vasculature in the central nervous system. Sci. Immunol. 4, eaav0492 (2019).","journal-title":"Sci. Immunol."},{"key":"17545_CR10","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.molmed.2018.04.003","volume":"24","author":"R Rua","year":"2018","unstructured":"Rua, R. & McGavern, D. B. Advances in meningeal immunity. Trends Mol. Med. 24, 542\u2013559 (2018).","journal-title":"Trends Mol. Med."},{"key":"17545_CR11","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Xiong, Y., Mahmood, A., Zhang, Z. G. & Chopp, M. Angiogenesis and functional recovery after traumatic brain injury. in Vascular Mechanisms in CNS Trauma 141\u2013156 (Springer New York, 2014).","DOI":"10.1007\/978-1-4614-8690-9_8"},{"key":"17545_CR12","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1177\/0271678X17701460","volume":"37","author":"A Salehi","year":"2017","unstructured":"Salehi, A., Zhang, J. H. & Obenaus, A. Response of the cerebral vasculature following traumatic brain injury. J. Cereb. Blood Flow. Metab. 37, 2320\u20132339 (2017).","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"17545_CR13","first-page":"298","volume":"11","author":"Y Xiong","year":"2010","unstructured":"Xiong, Y., Mahmood, A. & Chopp, M. Angiogenesis, neurogenesis and brain recovery of function following injury. Curr. Opin. Investig. Drugs 11, 298\u2013308 (2010).","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"17545_CR14","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/s41590-018-0086-2","volume":"19","author":"MV Russo","year":"2018","unstructured":"Russo, M. V., Latour, L. L. & McGavern, D. B. Distinct myeloid cell subsets promote meningeal remodeling and vascular repair after mild traumatic brain injury. Nat. Immunol. 19, 442\u2013452 (2018).","journal-title":"Nat. Immunol."},{"key":"17545_CR15","doi-asserted-by":"crossref","unstructured":"Labat-gest, V. & Tomasi, S. Photothrombotic ischemia: a minimally invasive and reproducible photochemical cortical lesion model for mouse stroke studies. J. Vis. Exp. 50370 (2013).","DOI":"10.3791\/50370"},{"key":"17545_CR16","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.neuropharm.2018.08.004","volume":"145","author":"RM Jha","year":"2019","unstructured":"Jha, R. M., Kochanek, P. M. & Simard, J. M. Pathophysiology and treatment of cerebral edema in traumatic brain injury. Neuropharmacology 145, 230\u2013246 (2019).","journal-title":"Neuropharmacology"},{"key":"17545_CR17","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/nrm.2016.87","volume":"17","author":"M Simons","year":"2016","unstructured":"Simons, M., Gordon, E. & Claesson-Welsh, L. Mechanisms and regulation of endothelial VEGF receptor signalling. Nat. Rev. Mol. Cell Biol. 17, 611\u2013625 (2016).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"17545_CR18","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/nrd.2016.278","volume":"16","author":"P Saharinen","year":"2017","unstructured":"Saharinen, P., Eklund, L. & Alitalo, K. Therapeutic targeting of the angiopoietin-TIE pathway. Nat. Rev. Drug Discov. 16, 635\u2013661 (2017).","journal-title":"Nat. Rev. Drug Discov."},{"key":"17545_CR19","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/j.cell.2009.03.025","volume":"137","author":"R Benedito","year":"2009","unstructured":"Benedito, R. et al. The notch ligands Dll4 and Jagged1 have opposing effects on angiogenesis. Cell 137, 1124\u20131135 (2009).","journal-title":"Cell"},{"key":"17545_CR20","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/nrm.2016.94","volume":"17","author":"SJ Bray","year":"2016","unstructured":"Bray, S. J. Notch signalling in context. Nat. Rev. Mol. Cell Biol. 17, 722\u2013735 (2016).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"17545_CR21","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.cell.2014.09.025","volume":"159","author":"K Okabe","year":"2014","unstructured":"Okabe, K. et al. Neurons limit angiogenesis by titrating VEGF in retina. Cell 159, 584\u2013596 (2014).","journal-title":"Cell"},{"key":"17545_CR22","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1681\/ASN.2010030295","volume":"21","author":"K Sison","year":"2010","unstructured":"Sison, K. et al. Glomerular structure and function require paracrine, not autocrine, VEGF-VEGFR-2 signaling. J. Am. Soc. Nephrol. 21, 1691\u20131701 (2010).","journal-title":"J. Am. Soc. Nephrol."},{"key":"17545_CR23","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1016\/j.celrep.2015.08.024","volume":"12","author":"S Savant","year":"2015","unstructured":"Savant, S. et al. The orphan receptor tie1 controls angiogenesis and vascular remodeling by differentially regulating tie2 in tip and stalk cells. Cell Rep. 12, 1761\u20131773 (2015).","journal-title":"Cell Rep."},{"key":"17545_CR24","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1084\/jem.20080134","volume":"205","author":"K Hozumi","year":"2008","unstructured":"Hozumi, K. et al. Delta-like 4 is indispensable in thymic environment specific for T cell development. J. Exp. Med. 205, 2507\u20132513 (2008).","journal-title":"J. Exp. Med."},{"key":"17545_CR25","doi-asserted-by":"crossref","first-page":"4754","DOI":"10.1182\/blood-2006-01-0141","volume":"107","author":"S B\u04d3umer","year":"2006","unstructured":"B\u04d3umer, S. et al. Vascular endothelial cell-specific phosphotyrosine phophatase (VE-PTP) activity is required for blood vessel development. Blood 107, 4754\u20134762 (2006).","journal-title":"Blood"},{"key":"17545_CR26","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms2683","volume":"4","author":"M Hayashi","year":"2013","unstructured":"Hayashi, M. et al. VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation. Nat. Commun. 4, 1672 (2013).","journal-title":"Nat. Commun."},{"key":"17545_CR27","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.devcel.2011.07.001","volume":"21","author":"A Armulik","year":"2011","unstructured":"Armulik, A., Genov\u00e9, G. & Betsholtz, C. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev. Cell 21, 193\u2013215 (2011).","journal-title":"Dev. Cell"},{"key":"17545_CR28","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1172\/JCI0215621","volume":"110","author":"A Uemura","year":"2002","unstructured":"Uemura, A. et al. Recombinant angiopoietin-1 restores higher-order architecture of growing blood vessels in mice in the absence of mural cells. J. Clin. Invest. 110, 1619\u20131628 (2002).","journal-title":"J. Clin. Invest."},{"key":"17545_CR29","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1002\/ana.25169","volume":"83","author":"AJ Schain","year":"2018","unstructured":"Schain, A. J. et al. Activation of pial and dural macrophages and dendritic cells by cortical spreading depression. Ann. Neurol. 83, 508\u2013521 (2018).","journal-title":"Ann. Neurol."},{"key":"17545_CR30","first-page":"e47","volume":"100","author":"C-H Cho","year":"2007","unstructured":"Cho, C.-H. et al. Angiogenic role of LYVE-1-positive macrophages in adipose tissue. Circ. Res. 100, e47\u2013e57 (2007).","journal-title":"Circ. Res."},{"key":"17545_CR31","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/s41590-018-0272-2","volume":"20","author":"SA Dick","year":"2019","unstructured":"Dick, S. A. et al. Self-renewing resident cardiac macrophages limit adverse remodeling following myocardial infarction. Nat. Immunol. 20, 29\u201339 (2019).","journal-title":"Nat. Immunol."},{"key":"17545_CR32","doi-asserted-by":"crossref","unstructured":"Chakarov, S. et al. Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches. Science 15, 363 (2019).","DOI":"10.1126\/science.aau0964"},{"key":"17545_CR33","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1111\/micc.12259","volume":"23","author":"BA Corliss","year":"2016","unstructured":"Corliss, B. A., Azimi, M. S., Munson, J. M., Peirce, S. M. & Murfee, W. L. Macrophages: an inflammatory link between angiogenesis and lymphangiogenesis. Microcirculation 23, 95\u2013121 (2016).","journal-title":"Microcirculation"},{"key":"17545_CR34","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.immuni.2016.02.015","volume":"44","author":"TA Wynn","year":"2016","unstructured":"Wynn, T. A. & Vannella, K. M. Macrophages in tissue repair, regeneration, and fibrosis. Immunity 44, 450\u2013462 (2016).","journal-title":"Immunity"},{"key":"17545_CR35","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1172\/JCI87442","volume":"127","author":"D Choi","year":"2017","unstructured":"Choi, D. et al. Laminar flow downregulates Notch activity to promote lymphatic sprouting. J. Clin. Invest. 127, 1225\u20131240 (2017).","journal-title":"J. Clin. Invest."},{"key":"17545_CR36","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0002-9440(10)63273-7","volume":"165","author":"T Inai","year":"2004","unstructured":"Inai, T. et al. Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am. J. Pathol. 165, 35\u201352 (2004).","journal-title":"Am. J. Pathol."},{"key":"17545_CR37","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/nrn3407","volume":"14","author":"Y Xiong","year":"2013","unstructured":"Xiong, Y., Mahmood, A. & Chopp, M. Animal models of traumatic brain injury. Nat. Rev. Neurosci. 14, 128\u2013142 (2013).","journal-title":"Nat. Rev. Neurosci."},{"key":"17545_CR38","first-page":"1325","volume":"6","author":"DR Namjoshi","year":"2013","unstructured":"Namjoshi, D. R. et al. Towards clinical management of traumatic brain injury: a review of models and mechanisms from a biomechanical perspective. Dis. Model. Mech. 6, 1325\u20131338 (2013).","journal-title":"Dis. Model. Mech."},{"key":"17545_CR39","doi-asserted-by":"crossref","first-page":"5332","DOI":"10.1007\/s12035-018-1454-5","volume":"56","author":"X Ma","year":"2019","unstructured":"Ma, X. et al. Animal models of traumatic brain injury and assessment of injury severity. Mol. Neurobiol. 56, 5332\u20135345 (2019).","journal-title":"Mol. Neurobiol."},{"key":"17545_CR40","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature14432","volume":"523","author":"A Louveau","year":"2015","unstructured":"Louveau, A. et al. Structural and functional features of central nervous system lymphatic vessels. Nature 523, 337\u2013341 (2015).","journal-title":"Nature"},{"key":"17545_CR41","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1084\/jem.20142290","volume":"212","author":"A Aspelund","year":"2015","unstructured":"Aspelund, A. et al. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J. Exp. Med. 212, 991\u2013999 (2015).","journal-title":"J. Exp. Med."},{"key":"17545_CR42","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/s41586-019-1419-5","volume":"572","author":"JH Ahn","year":"2019","unstructured":"Ahn, J. H. et al. Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid. Nature 572, 62\u201366 (2019).","journal-title":"Nature"},{"key":"17545_CR43","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1038\/jcbfm.2009.271","volume":"30","author":"O Thau-Zuchman","year":"2010","unstructured":"Thau-Zuchman, O., Shohami, E., Alexandrovich, A. G. & Leker, R. R. Vascular endothelial growth factor increases neurogenesis after traumatic brain injury. J. Cereb. Blood Flow. Metab. 30, 1008\u20131016 (2010).","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"17545_CR44","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1089\/neu.2010.1473","volume":"28","author":"KT Lu","year":"2011","unstructured":"Lu, K. T. et al. Hippocampal neurogenesis after traumatic brain injury is mediated by vascular endothelial growth factor receptor-2 and the Raf\/MEK\/ERK cascade. J. Neurotrauma 28, 441\u2013450 (2011).","journal-title":"J. Neurotrauma"},{"key":"17545_CR45","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.clineuro.2016.02.032","volume":"144","author":"M Li","year":"2016","unstructured":"Li, M. et al. The role of vascular endothelial growth factor and vascular endothelial growth inhibitor in clinical outcome of traumatic brain injury. Clin. Neurol. Neurosurg. 144, 7\u201313 (2016).","journal-title":"Clin. Neurol. Neurosurg."},{"key":"17545_CR46","doi-asserted-by":"crossref","unstructured":"Geiseler, S. J. & Morland, C. The janus face of VEGF in stroke. Int. J. Mol. Sci. 19, 1362 (2018).","DOI":"10.3390\/ijms19051362"},{"key":"17545_CR47","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1006\/dbio.1999.9355","volume":"212","author":"L Miquerol","year":"1999","unstructured":"Miquerol, L., Gertsenstein, M., Harpal, K., Rossant, J. & Nagy, A. Multiple developmental roles of VEGF suggested by a LacZ-tagged allele. Dev. Biol. 212, 307\u2013322 (1999).","journal-title":"Dev. Biol."},{"key":"17545_CR48","volume":"7","author":"Q Chen","year":"2016","unstructured":"Chen, Q. et al. Endothelial cells are progenitors of cardiac pericytes and vascular smooth muscle cells. Nat. Commun. 7, 12422 (2016).","journal-title":"Nat. Commun."},{"key":"17545_CR49","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1364\/BOE.6.002158","volume":"6","author":"H Seo","year":"2015","unstructured":"Seo, H., Hwang, Y., Choe, K. & Kim, P. In vivo quantitation of injected circulating tumor cells from great saphenous vein based on video-rate confocal microscopy. Biomed. Opt. Express 6, 2158 (2015).","journal-title":"Biomed. Opt. Express"},{"key":"17545_CR50","unstructured":"Han, S. et al. Amelioration of sepsis by TIE2 activation-induced vascular protection. Sci. Transl. Med. 8, 355ra55 (2016)."},{"key":"17545_CR51","doi-asserted-by":"crossref","unstructured":"Kokubu, H. & Lim, J. X-gal staining on adult mouse brain sections. Bio Protoc. 4, e1064 (2014).","DOI":"10.21769\/BioProtoc.1064"},{"key":"17545_CR52","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","volume":"177","author":"T Stuart","year":"2019","unstructured":"Stuart, T. et al. Comprehensive integration of single-cell data. Cell 177, 1888\u20131902.e21 (2019).","journal-title":"Cell"},{"key":"17545_CR53","doi-asserted-by":"crossref","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.e9 (2019).","journal-title":"Cell Syst."},{"key":"17545_CR54","doi-asserted-by":"crossref","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).","DOI":"10.1186\/s13059-015-0844-5"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-020-17545-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-020-17545-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-020-17545-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T00:20:48Z","timestamp":1670286048000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-020-17545-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,31]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["17545"],"URL":"https:\/\/doi.org\/10.1038\/s41467-020-17545-2","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,31]]},"assertion":[{"value":"10 December 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors have declared that no competing of interest exists.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3866"}}