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

Carlos Filipe Pereira, Betty Chang, Andreia Gomes, Jeffrey Bernitz, Dmitri Papatsenko, Xiaohong Niu, Gemma Swiers, Emanuele Azzoni, Marella F.T.R. de Bruijn, Christoph Schaniel, Ihor R. Lemischka, Kateri A. Moore

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

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.

Original languageEnglish
Pages (from-to)525-539
Number of pages15
JournalDevelopmental Cell
Volume36
Issue number5
DOIs
StatePublished - 7 Mar 2016

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