Journal
STEM CELLS
Volume 36, Issue 2, Pages 206-217Publisher
WILEY
DOI: 10.1002/stem.2739
Keywords
Single cell RNA-seq; Hemogenic endothelium; Human embryonic stem cells; Human hematopoiesis
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Funding
- NIH Grant: National Cancer Institute Grant [R01CA203348]
- NIH Grant: National Institute of Diabetes and Digestive and Kidney Diseases Grant [F30DK107071]
- NIH Grant: National Institute of General Medicine Sciences grant [T32GM113846, T32GM008244]
- Regenerative Medicine Minnesota program
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Endothelial-to-hematopoietic transition (EHT) is an important stage in definitive hematopoietic development. However, the genetic mechanisms underlying human EHT remain poorly characterized. We performed single cell RNA-seq using 55 hemogenic endothelial cells (HECs: CD31(+)CD144(+)CD41(-)CD43(-)CD45(-)CD73(-)RUNX1c(+)), 47 vascular endothelial cells without hematopoietic potential (non-HE: CD31(+)CD144(+)CD41(-)CD43(-)CD45(-)CD73(-)RUNX1c(-)), and 35 hematopoietic progenitor cells (HPCs: CD34(+)CD43(+)RUNX1c(+)) derived from human embryonic stem cells (hESCs). HE and HP were enriched in genes implicated in hemogenic endothelial transcriptional networks, such as ERG, GATA2, and FLI. We found transcriptional overlap between individual HECs and HPCs; however, these populations were distinct from non-HE. Further analysis revealed novel biomarkers for human HEC/HPCs, including TIMP3, ESAM, RHOJ, and DLL4. Collectively, we demonstrate that hESC-derived HE and HP share a common developmental pathway, while non-HE are more heterogeneous and transcriptionally distinct. Our findings provide a novel strategy to test new genetic targets and optimize the production of definitive hematopoietic cells from human pluripotent stem cells.
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