Portal de Periódicos da CAPES

PDGFRα+ Cells in Embryonic Stem Cell Cultures Represent the In Vitro Equivalent of the Pre-implantation Primitive Endoderm Precursors

2017; Elsevier BV; Volume: 8; Issue: 2 Linguagem: Inglês

10.1016/j.stemcr.2016.12.010

2213-6711

Antonio Lo Nigro, Anchel de Jaime‐Soguero, Rita Khoueiry, Dong Seong Cho, Giorgia Maria Ferlazzo, Ilaria Perini, Vanesa Abon Escalona, Xabier L. Aranguren, Susana M. Chuva de Sousa Lopes, Kian Peng Koh, Pier Giulio Conaldi, Wei-Shou Hu, An Zwijsen, Frederic Lluı́s, Catherine M. Verfaillie,

CRISPR and Genetic Engineering

In early mouse pre-implantation development, primitive endoderm (PrE) precursors are platelet-derived growth factor receptor alpha (PDGFRα) positive. Here, we demonstrated that cultured mouse embryonic stem cells (mESCs) express PDGFRα heterogeneously, fluctuating between a PDGFRα+ (PrE-primed) and a platelet endothelial cell adhesion molecule 1 (PECAM1)-positive state (epiblast-primed). The two surface markers can be co-detected on a third subpopulation, expressing epiblast and PrE determinants (double-positive). In vitro, these subpopulations differ in their self-renewal and differentiation capability, transcriptional and epigenetic states. In vivo, double-positive cells contributed to epiblast and PrE, while PrE-primed cells exclusively contributed to PrE derivatives. The transcriptome of PDGFRα+ subpopulations differs from previously described subpopulations and shows similarities with early/mid blastocyst cells. The heterogeneity did not depend on PDGFRα but on leukemia inhibitory factor and fibroblast growth factor signaling and DNA methylation. Thus, PDGFRα+ cells represent the in vitro counterpart of in vivo PrE precursors, and their selection from cultured mESCs yields pure PrE precursors.