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

Research output: Contribution to journalArticle

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.

Details

Authors
  • 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
External organisations
  • Icahn School of Medicine at Mount Sinai
  • University of Coimbra
  • University of Oxford
Original languageEnglish
Pages (from-to)525-539
Number of pages15
JournalDevelopmental Cell
Volume36
Issue number5
Publication statusPublished - 2016 Mar 7
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes