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

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

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)318-333
Number of pages16
JournalStem Cell Reports
Volume8
Issue number2
DOIs
StatePublished - Feb 14 2017

Keywords

  • PDGFRα+ subpopulations
  • embryonic stem cell heterogeneity
  • in vitro model of early blastocyst development
  • pre-implantation PrE precursors

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