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

Pereira, Carlos Filipe LU ; Chang, Betty; Gomes, Andreia; Bernitz, Jeffrey M.; Papatsenko, Dmitri; Niu, Xiaohong; Swiers, Gemma; Azzoni, Emanuele; de Bruijn, Marella F T R and Schaniel, Christoph, et al. (2016) In Developmental Cell 36(5). p.525-539
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... (More)

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.

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published
in
Developmental Cell
volume
36
issue
5
pages
15 pages
publisher
Cell Press
external identifiers
  • scopus:84959312876
ISSN
1534-5807
DOI
10.1016/j.devcel.2016.02.011
language
English
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no
id
bd8f8f62-7666-4bc6-b82c-6ebaf373e8da
date added to LUP
2017-10-02 17:25:25
date last changed
2017-10-12 08:57:25
@article{bd8f8f62-7666-4bc6-b82c-6ebaf373e8da,
  abstract     = {<p>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<sup>+</sup>Sca1<sup>+</sup>CD34<sup>+</sup>CD45<sup>-</sup> (PS34CD45<sup>-</sup>). 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<sup>-</sup> cells correlate with reprogrammed precursors and establish a hemogenic precursor cell molecular signature. PS34CD45<sup>-</sup> cells are also present in intra-embryonic hemogenic sites. After stromal co-culture, PS34CD45<sup>-</sup> 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.</p>},
  author       = {Pereira, Carlos Filipe and Chang, Betty and Gomes, Andreia and Bernitz, Jeffrey M. and Papatsenko, Dmitri and Niu, Xiaohong and Swiers, Gemma and Azzoni, Emanuele and de Bruijn, Marella F T R and Schaniel, Christoph and Lemischka, Ihor R. and Moore, Kateri A.},
  issn         = {1534-5807},
  language     = {eng},
  month        = {03},
  number       = {5},
  pages        = {525--539},
  publisher    = {Cell Press},
  series       = {Developmental Cell},
  title        = {Hematopoietic Reprogramming In Vitro Informs In Vivo Identification of Hemogenic Precursors to Definitive Hematopoietic Stem Cells},
  url          = {http://dx.doi.org/10.1016/j.devcel.2016.02.011},
  volume       = {36},
  year         = {2016},
}