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

First Author  Pereira CF Year  2016
Journal  Dev Cell Volume  36
Issue  5 Pages  525-39
PubMed ID  26954547 Mgi Jnum  J:356649
Mgi Id  MGI:7762741 Doi  10.1016/j.devcel.2016.02.011
Citation  Pereira CF, et al. (2016) Hematopoietic Reprogramming In Vitro Informs In Vivo Identification of Hemogenic Precursors to Definitive Hematopoietic Stem Cells. Dev Cell 36(5):525-39
abstractText  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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