Meso-Endothelial Bipotent Progenitors from Human Placenta Display Distinct Molecular and Cellular Identity

Abstract

Summary: The existence of bipotential precursors for both mesenchymal and endothelial stem/progenitor cells in human postnatal life is debated. Here, we hypothesized that such progenitors are present within the human term placenta. From a heterogeneous placental single-cell suspension, a directly flow-sorted CD45−CD34+CD144+CD31Lo population uniquely differentiated into both endothelial and mesenchymal colonies in limiting dilution culture assays. Of interest, these bipotent cells were in vessel walls but not in contact with the circulation. RNA sequencing and functional analysis demonstrated that Notch signaling was a key driver for endothelial and bipotential progenitor function. In contrast, the formation of mesenchymal cells from the bipotential population was not affected by TGFβ receptor inhibition, a classical pathway for endothelial-mesenchymal transition. This study reveals a bipotent progenitor phenotype in the human placenta at the cellular and molecular levels, giving rise to endothelial and mesenchymal cells ex vivo. : In this article, Khosrotehrani and colleagues isolated a bipotent progenitor from the human placenta that is able to give rise to both endothelial and mesenchymal cells ex vivo. This progenitor was characterized at the cellular and molecular level. They show that these progenitors were in vessel walls and functionally rely on Notch signaling for progenitor function. Keywords: bipotential precursors, placenta, endothelial progenitor cells, vascularization, mesenchymoangioblast, endothelial colony-forming cells, vascular development, stem cell niche, osteopontin, notch signalling