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

Dev Cell. 2016 Mar 7;36(5):525-39. doi: 10.1016/j.devcel.2016.02.011.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Cell Lineage / physiology*
  • Cells, Cultured
  • Cellular Reprogramming*
  • Endothelium / metabolism
  • Female
  • Fibroblasts / cytology
  • Hematopoiesis / genetics*
  • Hematopoietic Stem Cells / cytology*
  • Mice
  • Mice, Inbred C57BL
  • Mouse Embryonic Stem Cells / cytology*
  • Pregnancy