Erythroid/Myeloid Progenitors and Hematopoietic Stem Cells Originate from Distinct Populations of Endothelial Cells

MJ Chen, Yunlei Li, ME De Obaldia, Q Yang, AD Yzaguirre, T Yamada-Inagawa, Chris Vink, A Bhandoola, Elaine Dzierzak, NA Speck

Research output: Contribution to journalArticleAcademic

180 Citations (Scopus)

Abstract

Hematopoietic stem cells (HSCs) and an earlier wave of definitive erythroid/myeloid progenitors (EMPs) differentiate from hemogenic endothelial cells in the conceptus. EMPs can be generated in vitro from embryonic or induced pluripotent stem cells, but efforts to produce HSCs have largely failed. The formation of both EMPs and HSCs requires the transcription factor Runx1 and its non-DNA binding partner core binding factor beta (CBF beta). Here we show that the requirements for CBF beta in EMP and HSC formation in the conceptus are temporally and spatially distinct. Panendothelial expression of CBF beta in Tek-expressing cells was sufficient for EMP formation, but was not adequate for HSC formation. Expression of CBF beta in Ly6a-expressing cells, on the other hand, was sufficient for HSC, but not EMP, formation. The data indicate that EMPs and HSCs differentiate from distinct populations of hemogenic endothelial cells, with Ly6a expression specifically marking the HSC-generating hemogenic endothelium.
Original languageUndefined/Unknown
Pages (from-to)541-552
Number of pages12
JournalCell Stem Cell
Volume9
Issue number6
DOIs
Publication statusPublished - 2011

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