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Definitive hematopoiesis emerges via an endothelial-to-hematopoietic transition in the embryo and placenta; however, the precursor cells to hemogenic endothelium are not defined phenotypically. We previously demonstrated that the induction of hematopoietic progenitors from fibroblasts progresses through hemogenic precursors that are Prom1(+)Sca1(+)CD34(+)CD45(-) (PS34CD45(-)). Guided by these studies, we analyzed mouse placentas and identified a population with this phenotype. These cells express endothelial markers, are heterogeneous for early hematopoietic markers, and localize to the vascular labyrinth. Remarkably, global gene expression profiles of PS34CD45(-) cells correlate with reprogrammed precursors and establish a hemogenic precursor cell molecular signature. PS34CD45(-) cells are also present in intra-embryonic hemogenic sites. After stromal co-culture, PS34CD45(-) cells give rise to all blood lineages and engraft primary and secondary immunodeficient mice. In summary, we show that reprogramming reveals a phenotype for in vivo precursors to hemogenic endothelium, establishing that direct in vitro conversion informs developmental processes in vivo.

Original publication

DOI

10.1016/j.devcel.2016.02.011

Type

Journal article

Journal

Dev Cell

Publication Date

07/03/2016

Volume

36

Pages

525 - 539

Keywords

Animals, Cell Differentiation, Cell Lineage, Cells, Cultured, Cellular Reprogramming, Endothelium, Female, Fibroblasts, Hematopoiesis, Hematopoietic Stem Cells, Mice, Mice, Inbred C57BL, Mouse Embryonic Stem Cells, Pregnancy