Transcriptionally distinct mesenchymal stem/stromal cells circulate in fetus

Umbilical cord blood contains mesenchymal stem/stromal cells (MSCs) in addition to hematopoietic stem cells, serving as an attractive tool for regenerative medicine. As umbilical cord blood originates from fetus, abundant MSCs are expected to circulate in fetus. However, the properties of circulating MSCs in fetus have not been fully examined. In the present study, we aimed to analyze circulating MSCs, marked by the expression of platelet-derived growth factor receptor α (PDGFRα), during fetal development. Using PDGFRα GFP knock-in mice, we quantified the number of circulating PDGFRα positive MSCs during development. We further performed whole transcriptome analysis of circulating MSCs at single cell levels. We found that abundant PDGFRα positive cells circulate in embryo and diminish immediately after birth. In addition, single cell RNA-sequencing revealed transcriptional heterogeneity of MSCs in fetal circulation. These data lay a foundation to analyze the function of circulating MSCs during development. •Fetal circulation contains abundant PDGFRα MSC positive cells.•These PDGFRα positive cells diminish immediately after birth.•Circulating PDGFRα positive cells contain phenotypically distinct subpopulations.•PDGFRα positive cells may contribute to scar-less wound healing.•MSCs can be used to develop regenerative medicine.