Hematopoietic Reprogramming In Vitro Informs In Vivo Identification of Hemogenic Precursors to Definitive Hematopoietic Stem Cells

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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.


  • Carlos Filipe Pereira
  • Betty Chang
  • Andreia Gomes
  • Jeffrey M. Bernitz
  • Dmitri Papatsenko
  • Xiaohong Niu
  • Gemma Swiers
  • Emanuele Azzoni
  • Marella F T R de Bruijn
  • Christoph Schaniel
  • Ihor R. Lemischka
  • Kateri A. Moore
Externa organisationer
  • Icahn School of Medicine at Mount Sinai
  • University of Coimbra
  • University of Oxford
Sidor (från-till)525-539
Antal sidor15
TidskriftDevelopmental Cell
Utgåva nummer5
StatusPublished - 2016 mar 7
Peer review utfördJa
Externt publiceradJa