{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T16:56:31Z","timestamp":1788281791986,"version":"build-2803163510"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL142976"],"award-info":[{"award-number":["R01HL142976"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL091724"],"award-info":[{"award-number":["R01HL091724"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["20POST35200213"],"award-info":[{"award-number":["20POST35200213"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"abstract":"<jats:p>Definitive hematopoietic stem and progenitor cells (HSPCs) arise from a small number of hemogenic endothelial cells (HECs) within the developing embryo. Understanding the origin and ontogeny of HSPCs is of considerable interest and potential therapeutic value. It has been proposed that the murine placenta contains HECs that differentiate into HSPCs. However, during human gestation HSPCs arise in the aorta considerably earlier than when they can first be detected in the placenta, suggesting that the placenta may primarily serve as a niche. We found that the Runx1 transcription factor, which is required to generate HSPCs from HECs, is not expressed by mouse placental ECs. To definitively determine whether the mouse placenta is a site of HSPC emergence, we performed lineage tracing experiments with a Hoxa13<jats:sup>Cre<\/jats:sup> allele that specifically labels ECs in the placenta and umbilical cord (UC), but not in the yolk sac or embryo. Immunostaining revealed Hoxa13<jats:sup>Cre<\/jats:sup> lineage-traced HECs and HSPCs in the UC, a known site of HECs, but not the placenta. Consistent with these findings, ECs harvested from the E10.5 aorta and UC, but not the placenta, gave rise to hematopoietic cells ex vivo, while colony forming assays using E14.5 fetal liver revealed only 2% of HSPCs arose from Hoxa13-expressing precursors. In contrast, the pan-EC Cdh5-CreER<jats:sup>T2<\/jats:sup> allele labeled most HSPCs in the mouse placenta. Lastly, we found that RUNX1 and other HEC genes were not expressed in first-trimester human placenta villous ECs, suggesting that human placenta is not hemogenic. Our findings demonstrate that the placenta functions as a site for expansion of HSPCs that arise within the embryo proper and is not a primary site of HSPC emergence.<\/jats:p>","DOI":"10.1371\/journal.pbio.3003003","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T18:53:03Z","timestamp":1738090383000},"page":"e3003003","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Lineage tracing studies suggest that the placenta is not a de novo source of hematopoietic stem cells"],"prefix":"10.1371","volume":"23","author":[{"given":"Xiaowen","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Tober","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Dominguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan T.","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna","family":"Bockman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jisheng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sneha","family":"Mani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin Nien","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Triloshan","family":"Thillaikumaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Mericko-Ishizuka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Mainigi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy A.","family":"Speck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6489-7086","authenticated-orcid":true,"given":"Mark L.","family":"Kahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"issue":"2","key":"pbio.3003003.ref001","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/ni1560","article-title":"Of lineage and legacy: the development of mammalian hematopoietic stem cells","volume":"9","author":"E Dzierzak","year":"2008","journal-title":"Nat Immunol"},{"issue":"1","key":"pbio.3003003.ref002","doi-asserted-by":"crossref","first-page":"5405","DOI":"10.1038\/s41467-018-07769-8","article-title":"Murine hematopoietic stem cell activity is derived from pre-circulation embryos but not yolk sacs","volume":"9","author":"M Ganuza","year":"2018","journal-title":"Nat Commun"},{"issue":"5","key":"pbio.3003003.ref003","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.stem.2012.07.004","article-title":"Mouse embryonic head as a site for hematopoietic stem cell development","volume":"11","author":"Z Li","year":"2012","journal-title":"Cell Stem Cell"},{"issue":"6","key":"pbio.3003003.ref004","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1084\/jem.20102419","article-title":"Hierarchical organization and early hematopoietic specification of the developing HSC lineage in the AGM region","volume":"208","author":"S Rybtsov","year":"2011","journal-title":"J Exp Med"},{"issue":"4","key":"pbio.3003003.ref005","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1097\/MOH.0b013e328339f295","article-title":"Placenta as a newly identified source of hematopoietic stem cells","volume":"17","author":"LK Lee","year":"2010","journal-title":"Curr Opin Hematol"},{"issue":"4","key":"pbio.3003003.ref006","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.cell.2008.01.025","article-title":"Hematopoiesis: an evolving paradigm for stem cell biology","volume":"132","author":"SH Orkin","year":"2008","journal-title":"Cell"},{"issue":"3","key":"pbio.3003003.ref007","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.devcel.2004.12.016","article-title":"The placenta is a niche for hematopoietic stem cells","volume":"8","author":"C Gekas","year":"2005","journal-title":"Dev Cell"},{"issue":"4","key":"pbio.3003003.ref008","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.stem.2009.08.020","article-title":"Human placenta is a potent hematopoietic niche containing hematopoietic stem and progenitor cells throughout development","volume":"5","author":"C Robin","year":"2009","journal-title":"Cell Stem Cell"},{"issue":"3","key":"pbio.3003003.ref009","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.devcel.2005.02.001","article-title":"The murine placenta contains hematopoietic stem cells within the vascular labyrinth region","volume":"8","author":"K Ottersbach","year":"2005","journal-title":"Dev Cell"},{"issue":"2\u20133","key":"pbio.3003003.ref010","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1387\/ijdb.041938fd","article-title":"Commitment of hematopoietic stem cells in avian and mammalian embryos: an ongoing story","volume":"49","author":"F Dieterlen-Li\u00e8vre","year":"2005","journal-title":"Int J Dev Biol"},{"issue":"21","key":"pbio.3003003.ref011","doi-asserted-by":"crossref","first-page":"4183","DOI":"10.1242\/dev.02596","article-title":"The allantois and chorion, when isolated before circulation or chorio-allantoic fusion, have hematopoietic potential","volume":"133","author":"BM Zeigler","year":"2006","journal-title":"Development"},{"issue":"2","key":"pbio.3003003.ref012","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.ydbio.2006.08.069","article-title":"Hematopoietic potential of the pre-fusion allantois","volume":"301","author":"C Corbel","year":"2007","journal-title":"Dev Biol"},{"issue":"4","key":"pbio.3003003.ref013","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1073\/pnas.95.4.1641","article-title":"Blood-borne seeding by hematopoietic and endothelial precursors from the allantois","volume":"95","author":"A Caprioli","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"22","key":"pbio.3003003.ref014","doi-asserted-by":"crossref","first-page":"4507","DOI":"10.1242\/dev.125.22.4507","article-title":"Vascularization in the murine allantois occurs by vasculogenesis without accompanying erythropoiesis","volume":"125","author":"KM Downs","year":"1998","journal-title":"Development"},{"issue":"7","key":"pbio.3003003.ref015","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1096\/fj.00-0696fje","article-title":"Targeted inactivation of the sodium-calcium exchanger (Ncx1) results in the lack of a heartbeat and abnormal myofibrillar organization","volume":"15","author":"SV Koushik","year":"2001","journal-title":"FASEB J"},{"issue":"10","key":"pbio.3003003.ref016","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1387\/ijdb.093051cw","article-title":"A novel mutant allele of Ncx1: a single amino acid substitution leads to cardiac dysfunction","volume":"54","author":"C Wansleeben","year":"2010","journal-title":"Int J Dev Biol"},{"issue":"3","key":"pbio.3003003.ref017","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.stem.2008.01.001","article-title":"The emergence of hematopoietic stem cells is initiated in the placental vasculature in the absence of circulation","volume":"2","author":"KE Rhodes","year":"2008","journal-title":"Cell Stem Cell"},{"issue":"2","key":"pbio.3003003.ref018","doi-asserted-by":"crossref","first-page":"dev139691","DOI":"10.1242\/dev.139691","article-title":"The hematopoietic stem cell niche: from embryo to adult","volume":"145","author":"X Gao","year":"2018","journal-title":"Development"},{"issue":"3","key":"pbio.3003003.ref019","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.stem.2008.02.013","article-title":"Are hematopoietic stem cells generated in the placenta?","volume":"2","author":"A Kieusseian","year":"2008","journal-title":"Cell Stem Cell"},{"issue":"1\u20132","key":"pbio.3003003.ref020","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.cell.2014.12.032","article-title":"Hematopoietic stem cell arrival triggers dynamic remodeling of the perivascular niche","volume":"160","author":"OJ Tamplin","year":"2015","journal-title":"Cell"},{"issue":"12","key":"pbio.3003003.ref021","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1084\/jem.20111688","article-title":"Highly potent human hematopoietic stem cells first emerge in the intraembryonic aorta-gonad-mesonephros region","volume":"208","author":"A Ivanovs","year":"2011","journal-title":"J Exp Med"},{"key":"pbio.3003003.ref022","first-page":"2141475","article-title":"Understanding the journey of human hematopoietic stem cell development","author":"A Kumar","year":"2019","journal-title":"Stem Cells Int"},{"issue":"5","key":"pbio.3003003.ref023","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.stem.2013.10.010","article-title":"Deciphering hematopoietic stem cells in their niches: a critical appraisal of genetic models, lineage tracing, and imaging strategies","volume":"13","author":"C Joseph","year":"2013","journal-title":"Cell Stem Cell"},{"key":"pbio.3003003.ref024","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.ceb.2018.01.002","article-title":"Tracking the origin, development, and differentiation of hematopoietic stem cells","volume":"49","author":"PR Dharampuriya","year":"2017","journal-title":"Curr Opin Cell Biol"},{"issue":"2","key":"pbio.3003003.ref025","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1042\/BST20180320","article-title":"Endothelial-to-haematopoietic transition: an update on the process of making blood","volume":"47","author":"K Ottersbach","year":"2019","journal-title":"Biochem Soc Trans"},{"issue":"23","key":"pbio.3003003.ref026","doi-asserted-by":"crossref","first-page":"2652-2660.e3","DOI":"10.1016\/j.devcel.2022.11.003","article-title":"Mouse placenta fetal macrophages arise from endothelial cells outside the placenta","volume":"57","author":"X Chen","year":"2022","journal-title":"Dev Cell"},{"issue":"10","key":"pbio.3003003.ref027","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1038\/s41556-022-00999-5","article-title":"Murine foetal liver supports limited detectable expansion of life-long haematopoietic progenitors","volume":"24","author":"M Ganuza","year":"2022","journal-title":"Nat Cell Biol"},{"issue":"8","key":"pbio.3003003.ref028","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1242\/dev.131193","article-title":"Concealed expansion of immature precursors underpins acute burst of adult HSC activity in foetal liver","volume":"143","author":"S Rybtsov","year":"2016","journal-title":"Development"},{"issue":"4","key":"pbio.3003003.ref029","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.stemcr.2014.02.001","article-title":"Identification of multipotent progenitors that emerge prior to hematopoietic stem cells in embryonic development","volume":"2","author":"MA Inlay","year":"2014","journal-title":"Stem Cell Reports"},{"issue":"7231","key":"pbio.3003003.ref030","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/nature07619","article-title":"Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter","volume":"457","author":"MJ Chen","year":"2009","journal-title":"Nature"},{"issue":"1","key":"pbio.3003003.ref031","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s00441-015-2174-z","article-title":"Differential expression and regulation of Runx1 in mouse uterus during the peri-implantation period","volume":"362","author":"ZK Bai","year":"2015","journal-title":"Cell Tissue Res"},{"issue":"Suppl_1","key":"pbio.3003003.ref032","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1093\/biolreprod\/85.s1.180","article-title":"Runx1 functions downstream of BMP2 to regulate uterine stromal differentiation and blood vessel formation at the maternal-fetal interface","volume":"85","author":"K Athilakshmi","year":"2011","journal-title":"Biol Reprod"},{"key":"pbio.3003003.ref033","doi-asserted-by":"crossref","first-page":"e60266","DOI":"10.7554\/eLife.60266","article-title":"Single nuclei RNA-seq of mouse placental labyrinth development","volume":"9","author":"B Marsh","year":"2020","journal-title":"Elife"},{"issue":"7","key":"pbio.3003003.ref034","doi-asserted-by":"crossref","first-page":"108758","DOI":"10.1016\/j.celrep.2021.108758","article-title":"SOX17 integrates HOXA and arterial programs in hemogenic endothelium to drive definitive lympho-myeloid hematopoiesis","volume":"34","author":"HS Jung","year":"2021","journal-title":"Cell Rep"},{"issue":"1","key":"pbio.3003003.ref035","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.stemcr.2018.05.002","article-title":"GATA2 is dispensable for specification of hemogenic endothelium but promotes endothelial-to-hematopoietic transition","volume":"11","author":"H Kang","year":"2018","journal-title":"Stem Cell Reports"},{"issue":"Suppl 1","key":"pbio.3003003.ref036","doi-asserted-by":"crossref","first-page":"S61","DOI":"10.1016\/j.placenta.2017.05.005","article-title":"GATA factors: master regulators of gene expression in trophoblast progenitors","volume":"60","author":"S Paul","year":"2017","journal-title":"Placenta"},{"key":"pbio.3003003.ref037","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1038\/ncomms3609","article-title":"Sox17 is indispensable for acquisition and maintenance of arterial identity","volume":"4","author":"M Corada","year":"2013","journal-title":"Nat Commun"},{"issue":"2","key":"pbio.3003003.ref038","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1182\/blood-2011-10-386094","article-title":"GFI1 and GFI1B control the loss of endothelial identity of hemogenic endothelium during hematopoietic commitment","volume":"120","author":"C Lancrin","year":"2012","journal-title":"Blood"},{"issue":"12","key":"pbio.3003003.ref039","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1182\/blood-2009-11-252635","article-title":"Hey2 acts upstream of Notch in hematopoietic stem cell specification in zebrafish embryos","volume":"116","author":"JM Rowlinson","year":"2010","journal-title":"Blood"},{"issue":"4","key":"pbio.3003003.ref040","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1242\/dev.075408","article-title":"Recruitment of 5\u2019 Hoxa genes in the allantois is essential for proper extra-embryonic function in placental mammals","volume":"139","author":"M Scotti","year":"2012","journal-title":"Development"},{"issue":"5","key":"pbio.3003003.ref041","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.stem.2012.07.018","article-title":"The transcriptional landscape of hematopoietic stem cell ontogeny","volume":"11","author":"S McKinney-Freeman","year":"2012","journal-title":"Cell Stem Cell"},{"issue":"12","key":"pbio.3003003.ref042","doi-asserted-by":"crossref","first-page":"3988","DOI":"10.1182\/blood-2005-05-2003","article-title":"Loss of expression of the Hoxa-9 homeobox gene impairs the proliferation and repopulating ability of hematopoietic stem cells","volume":"106","author":"HJ Lawrence","year":"2005","journal-title":"Blood"},{"issue":"6","key":"pbio.3003003.ref043","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.stem.2008.09.018","article-title":"Fate tracing reveals the endothelial origin of hematopoietic stem cells","volume":"3","author":"AC Zovein","year":"2008","journal-title":"Cell Stem Cell"},{"issue":"2","key":"pbio.3003003.ref044","doi-asserted-by":"crossref","first-page":"dev158162","DOI":"10.1242\/dev.158162","article-title":"Runx1 is sufficient for blood cell formation from non-hemogenic endothelial cells in vivo only during early embryogenesis","volume":"145","author":"AD Yzaguirre","year":"2018","journal-title":"Development"},{"issue":"7","key":"pbio.3003003.ref045","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.1182\/blood-2003-07-2439","article-title":"Role of RUNX1 in adult hematopoiesis: analysis of RUNX1-IRES-GFP knock-in mice reveals differential lineage expression","volume":"103","author":"RB Lorsbach","year":"2004","journal-title":"Blood"},{"issue":"22","key":"pbio.3003003.ref046","doi-asserted-by":"crossref","first-page":"5680","DOI":"10.1182\/blood-2008-08-174508","article-title":"DLL1-mediated Notch activation regulates endothelial identity in mouse fetal arteries","volume":"113","author":"I S\u00f6rensen","year":"2009","journal-title":"Blood"},{"issue":"6","key":"pbio.3003003.ref047","doi-asserted-by":"crossref","first-page":"1160-1171.e5","DOI":"10.1016\/j.immuni.2018.04.025","article-title":"Hemogenic endothelial fate mapping reveals dual developmental origin of mast cells","volume":"48","author":"R Gentek","year":"2018","journal-title":"Immunity"},{"key":"pbio.3003003.ref048","doi-asserted-by":"crossref","first-page":"e77241","DOI":"10.7554\/eLife.77241","article-title":"VE-cadherin enables trophoblast endovascular invasion and spiral artery remodeling during placental development","volume":"11","author":"DC Sung","year":"2022","journal-title":"Elife"},{"key":"pbio.3003003.ref049","doi-asserted-by":"crossref","first-page":"eaau4788","DOI":"10.1126\/sciadv.aau4788","article-title":"A single-cell survey of the human first-trimester placenta and decidua","volume":"4","author":"H Suryawanshi","year":"2018","journal-title":"Sci Adv"},{"issue":"7906","key":"pbio.3003003.ref050","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1038\/s41586-022-04571-x","article-title":"Mapping human haematopoietic stem cells from haemogenic endothelium to birth","volume":"604","author":"V Calvanese","year":"2022","journal-title":"Nature"},{"key":"pbio.3003003.ref051","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.placenta.2019.03.015","article-title":"Aldehyde dehydrogenase isoforms and inflammatory cell populations are differentially expressed in term human placentas affected by intrauterine growth restriction","volume":"81","author":"A Chu","year":"2019","journal-title":"Placenta"},{"issue":"6\u20137","key":"pbio.3003003.ref052","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1387\/ijdb.103070cg","article-title":"Hematopoietic stem cell development in the placenta","volume":"54","author":"C Gekas","year":"2010","journal-title":"Int J Dev Biol"},{"issue":"5","key":"pbio.3003003.ref053","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/j.stemcr.2020.03.020","article-title":"Transcriptome dynamics of hematopoietic stem cell formation revealed using a combinatorial Runx1 and Ly6a reporter system","volume":"14","author":"MJ Chen","year":"2020","journal-title":"Stem Cell Reports"},{"issue":"1","key":"pbio.3003003.ref054","doi-asserted-by":"crossref","first-page":"e136542","DOI":"10.1172\/JCI136542","article-title":"Macrophage-derived netrin-1 drives adrenergic nerve-associated lung fibrosis","volume":"131","author":"R Gao","year":"2021","journal-title":"J Clin Invest"},{"issue":"1","key":"pbio.3003003.ref055","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s12915-022-01275-6","article-title":"A method for ultrafast tissue clearing that preserves fluorescence for multimodal and longitudinal brain imaging","volume":"20","author":"QH Shan","year":"2022","journal-title":"BMC Biol"},{"key":"pbio.3003003.ref056","article-title":"Isolation and analysis of hematopoietic stem cells from the placenta.","author":"O Gekas","year":"2008","journal-title":"J Vis Exp"},{"issue":"7","key":"pbio.3003003.ref057","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1182\/blood.2020004801","article-title":"Developmental trajectory of prehematopoietic stem cell formation from endothelium","volume":"136","author":"Q Zhu","year":"2020","journal-title":"Blood"},{"issue":"1\u20132","key":"pbio.3003003.ref058","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.jim.2009.06.008","article-title":"ELDA: extreme limiting dilution analysis for comparing depleted and enriched populations in stem cell and other assays","volume":"347","author":"Y Hu","year":"2009","journal-title":"J Immunol Methods"},{"key":"pbio.3003003.ref059","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Y Hao","year":"2021","journal-title":"Cell"}],"container-title":["PLOS Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3003003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T18:53:32Z","timestamp":1738090412000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3003003"}},"subtitle":[],"editor":[{"given":"Sally","family":"Lowell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,1,28]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pbio.3003003","relation":{},"ISSN":["1545-7885"],"issn-type":[{"value":"1545-7885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,28]]}}}