Meso-Endothelial bipotent progenitors from human placenta display distinct molecular and cellular identity.

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, 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 signalling 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 TGFbeta 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 level, giving rise to endothelial and mesenchymal cells ex-vivo.RNA-sequencing was performed on the three placental populations with high colony forming potential, mesenchymal stem/stromal cells (CD45-CD34+CD31-), Meso-Endothelial bipotent progenitors (CD45-CD34+CD31Low), and endothelial colony forming cells (CD45-CD34+CD31Int).