Project description:The heterogeneity of embryonic endothelial cells (ECs) especially the distinction of arteriovenous ECs remains incompletely characterized. We established a mouse single-EC transcriptomic landscape at mid-to-late gestation stage and identified 19 subclusters, including Etv2+Bnip3+ early ECs and 2 specialized ECs. Most of these subtypes were grouped by their vascular-bed types, while ECs from brain, heart and liver were grouped by their tissue origins. Unlike arterial ECs (aECs), embryonic venous (vECs) and capillary ECs (cECs) shared less markers with their adult counterparts. Notably, capillary clusters showed some venous characteristics and one of them served as an intermediate state of arteriovenous specification. Compared to the more early stage, a clear arteriovenous branch which also going through a venous plexus was identified. aECs and vECs showed distinct transcriptional modules including specific regulatory networks of transcription factors. Especially, USF1 and MECOM were verified functioning in arteriovenous differentiation through human induced pluripotent stem cells (hiPSC) differentiation models. We therefore provide a new map of endothelial heterogeneity highlighting regulation of arteriovenous specification.
Project description: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.
Project description:The goal of this study was to gain insight into the molecular heterogeneity of capillary endothelial cells derived from different organs by microarray profiling of freshly isolated cells and identify transcription factors that may determine the specific gene expression profile of endothelial cells from different tissues. The study focused on heart endothelial cells and presents a validated signature of 31 genes that are highly enriched in heart endothelial cells. Within this signature 5 transcription factors were identified and the optimal combination of these transcription factors was determined for specification of the heart endothelial fingerprint. From three tissue types (mouse brain, heart and liver), we collected five freshly isolated endothelial cell samples each. For each brain sample we pooled RNA from 6 mice. For each heart sample we pooled RNA from 4 mice. For each liver sample we pooled RNA from 2 mice. The three endothelial subtypes were then compared. For each subtype, specific gene profiles were defined by determining the genes that were highly enriched versus the other two endothelial subtypes.
Project description:The goal of this study was to gain insight into the molecular heterogeneity of capillary endothelial cells derived from different organs by microarray profiling of freshly isolated cells and identify transcription factors that may determine the specific gene expression profile of endothelial cells from different tissues. The study focused on heart endothelial cells and presents a validated signature of 31 genes that are highly enriched in heart endothelial cells. Within this signature 5 transcription factors were identified and the optimal combination of these transcription factors was determined for specification of the heart endothelial fingerprint.
Project description:Pulmonary endothelial cells are an essential component of the lung alveolus, where they assist in integrating this niche with the cardiovascular system to perform gas exchange with the external environment. Despite its importance, the extent and function of endothelial cell heterogeneity within the lung remains incompletely understood. Using single-cell analytics, we show that multiple vascular endothelial cell populations exist in the mouse lung, including macrovascular endothelium (maECs), microvascular endothelium (miECs), and a new population we have termed regulator endothelium (RECs). RECs express a unique gene signature including elevated expression of Cd34 (Cd34high), Vegfr2 (Kdr), Ednrb, and Car4. The location of RECs within the lung is similar to other miECs at homeostasis, but they appear to preferentially invest regions of regenerating lung tissue after acute lung injury. Receptor-ligand analysis indicates that RECs are primed to receive reparative signals from alveolar type I cells through Vegfa-Vegfr2. Interestingly, influenza infection reveals the emergence of a highly proliferative endothelial cell population (PECs) that likely contributes to revascularization of the alveolar space after injury and may arise from Cd34low miECs. These studies map endothelial cell heterogeneity in the adult lung and characterize the preferential response of novel endothelial cell subpopulations required for proper tissue regeneration after acute lung injury.