TY - JOUR
T1 - Hematopoietic Reprogramming In Vitro Informs In Vivo Identification of Hemogenic Precursors to Definitive Hematopoietic Stem Cells
AU - Pereira, Carlos Filipe
AU - Chang, Betty
AU - Gomes, Andreia
AU - Bernitz, Jeffrey
AU - Papatsenko, Dmitri
AU - Niu, Xiaohong
AU - Swiers, Gemma
AU - Azzoni, Emanuele
AU - de Bruijn, Marella F.T.R.
AU - Schaniel, Christoph
AU - Lemischka, Ihor R.
AU - Moore, Kateri A.
N1 - Funding Information:
We thank N. Speck (University of Pennsylvania) for the OP9 cell lines. We thank the members of the Lemischka and Moore laboratories for useful discussions and Y. Liu for laboratory management. We would like to thank V. Gouon-Evans, O. Goldman, S. Ghaffari, G. Camprecios, and P. Rimmele for assistance. We thank J. Kovacic and A. Nomura-Kitabayashi for the R26StopYFP mice and advice with lineage tracing and H. Schöler for critical reading of the manuscript. We would also like to thank the Mount Sinai Pluripotent Stem Cell Core and S.L. D'Souza for help with materials and protocols and the Mount Sinai Genomics, Flow Cytometry and Mouse facilities. This study was made possible in part by funds granted by the Charles H. Revson Foundation (C.F.P., senior fellow in biomedical science) and by NIH 1R01HL119404 (K.A.M. and I.R.L.). The statements made and views expressed are solely the responsibility of the authors.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/3/7
Y1 - 2016/3/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84959312876&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2016.02.011
DO - 10.1016/j.devcel.2016.02.011
M3 - Article
C2 - 26954547
AN - SCOPUS:84959312876
SN - 1534-5807
VL - 36
SP - 525
EP - 539
JO - Developmental Cell
JF - Developmental Cell
IS - 5
ER -