Single-cell transcriptome Atlas reveals embryonic endothelial heterogeneity

Mature endothelial cells (ECs) are heterogeneous, with subtypes defined by tissue origin and by position within the vascular bed. Here, we performed scRNA-seq with mouse embryonic ECs and identified 19 subclusters, including Etv2+Bnip3+ early EC progenitors. Most of these subtypes were grouped by their vascular-bed types, while ECs from brain, heart and liver were grouped by their tissue origins. Compared to arterial ECs (aECs), embryonic venous (vECs) and capillary ECs (cECs) shared less markers with their adult counterparts. cECs showed some venous characteristics. One cEC cluster with both venous and capillary features served as a branch point for aEC and vEC lineages. aECs and vECs showed distinct transcriptional regulatory networks. Cdh5(PAC)-CreERT2 mice were bred with R26mTmG mice. After tamoxifen induction, ECs were enriched from E9.5, E12.5 and E15.5 embryos by magnetic-activated cell sorting (MACS), then scRNA-seq was performed with droplet-based tool (10x Genomics).