{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Fowler JL"],"funding":["Bill & Melinda Gates Foundation","Human Frontier Science Program","PEW Charitable Trusts","Ludwig Cancer Research","NHLBI NIH HHS","California Institute for Regenerative Medicine","NIH","JDRF","David and Lucile Packard Foundation","NIGMS NIH HHS","NIH HHS","Japan Society for the Promotion of Science"],"pagination":["1110-1131.e22"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11072092"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["59(9)"],"pubmed_abstract":["The developmental origin of blood-forming hematopoietic stem cells (HSCs) is a longstanding question. Here, our non-invasive genetic lineage tracing in mouse embryos pinpoints that artery endothelial cells generate HSCs. Arteries are transiently competent to generate HSCs for 2.5 days (∼E8.5-E11) but subsequently cease, delimiting a narrow time frame for HSC formation in vivo. Guided by the arterial origins of blood, we efficiently and rapidly differentiate human pluripotent stem cells (hPSCs) into posterior primitive streak, lateral mesoderm, artery endothelium, hemogenic endothelium, and >90% pure hematopoietic progenitors within 10 days. hPSC-derived hematopoietic progenitors generate T, B, NK, erythroid, and myeloid cells in vitro and, critically, express hallmark HSC transcription factors HLF and HOXA5-HOXA10, which were previously challenging to upregulate. We differentiated hPSCs into highly enriched HLF+ HOXA+ hematopoietic progenitors with near-stoichiometric efficiency by blocking formation of unwanted lineages at each differentiation step. hPSC-derived HLF+ HOXA+ hematopoietic progenitors could avail both basic research and cellular therapies."],"journal":["Developmental cell"],"pubmed_title":["Lineage-tracing hematopoietic stem cell origins in vivo to efficiently make human HLF+ HOXA+ hematopoietic progenitors from pluripotent stem cells."],"pmcid":["PMC11072092"],"funding_grant_id":["DP5 OD024558","R01 HL147124","R01 HL128503","R01 HL142637","S10 OD026962","T32 HL120824","R35 GM133482"],"pubmed_authors":["Loh KM","Liu DD","Luca VC","Ang LT","Majeti R","Miquerol L","Porteus MH","Xiong X","Mason C","Nakauchi H","Karigane D","Chai T","Niizuma K","Nishimura T","Zheng SL","Cromer MK","Weissman IL","Yilmaz L","Kayamori K","Gonzalez-Perez D","Chen A","Banuelos AM","Fowler JL","Nguyen A","Chen JY","Red-Horse K"],"additional_accession":[]},"is_claimable":false,"name":"Lineage-tracing hematopoietic stem cell origins in vivo to efficiently make human HLF+ HOXA+ hematopoietic progenitors from pluripotent stem cells.","description":"The developmental origin of blood-forming hematopoietic stem cells (HSCs) is a longstanding question. Here, our non-invasive genetic lineage tracing in mouse embryos pinpoints that artery endothelial cells generate HSCs. Arteries are transiently competent to generate HSCs for 2.5 days (∼E8.5-E11) but subsequently cease, delimiting a narrow time frame for HSC formation in vivo. Guided by the arterial origins of blood, we efficiently and rapidly differentiate human pluripotent stem cells (hPSCs) into posterior primitive streak, lateral mesoderm, artery endothelium, hemogenic endothelium, and >90% pure hematopoietic progenitors within 10 days. hPSC-derived hematopoietic progenitors generate T, B, NK, erythroid, and myeloid cells in vitro and, critically, express hallmark HSC transcription factors HLF and HOXA5-HOXA10, which were previously challenging to upregulate. We differentiated hPSCs into highly enriched HLF+ HOXA+ hematopoietic progenitors with near-stoichiometric efficiency by blocking formation of unwanted lineages at each differentiation step. hPSC-derived HLF+ HOXA+ hematopoietic progenitors could avail both basic research and cellular therapies.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-06-01T17:26:06.274Z","creation":"2026-04-08T14:12:06.393Z"},"accession":"S-EPMC11072092","cross_references":{"pubmed":["38569552"],"doi":["10.1016/j.devcel.2024.03.003"]}}