Project description:The heterogeneity of endothelial cells (ECs), lining blood vessels, across tissues remains incompletely inventoried. We constructed an atlas of >32,000 single-EC transcriptomic data from 11 tissues of the model organism Mus musculus. We propose a new classification of EC phenotypes based on transcriptome signatures and inferred putative biological features. We identified top-ranking markers for ECs from each tissue. ECs from different vascular beds (arteries, capillaries, veins, lymphatics) resembled each other across tissues, but only arterial, venous and lymphatic (not capillary) ECs shared markers, illustrating a greater heterogeneity of capillary ECs. We identified high-endothelial-venule and lacteal-like ECs in the intestines, and angiogenic ECs in healthy tissues. Metabolic transcriptomes of ECs differed amongst spleen, lung, liver, brain and testis, while being similar for kidney, heart, muscle and intestines. Within tissues, metabolic gene expression was heterogeneous amongst ECs from different vascular beds, altogether highlighting large EC heterogeneity.
Project description:We previously identified somatic activating KRAS mutations in a majority of human arteriovenous malformations (AVMs), using whole exome sequencing, which were enhanced in AVM endothelial cell fractions. We have now performed whole genome sequencing on AVM endothelial and non-endothelial cell fractions, as well as paired blood samples, in order to identify further somatic mutations.
Project description:Three different cell types constitute the glomerular filter: mesangial cells, endothelial cells, and podocytes. As yet, it remains unknown to what extent cellular heterogeneity exists within healthy glomerular cell populations. Here, we used nanodroplet-based, highly parallel transcriptional profiling to characterize the cellular content of purified wildtype mouse glomeruli. Unsupervised clustering of 13,000 single-cell transcriptomes identified the three known glomerular cell types. We provide a comprehensive online atlas of gene expression in glomerular cells, which can be queried and visualized using an interactive and freely available database. Novel marker genes for all glomerular cell types were identified and supported by immunohistochemistry stainings obtained from the Human Protein Atlas. Subclustering of glomerular endothelial cells revealed a subset of activated endothelium, expressing marker genes related to endothelial proliferation. Additionally, the podocyte population could be divided in three different subclusters. In conclusion, our study comprehensively characterizes gene expression in individual glomerular cells and sets the stage for the dissection of glomerular function at the single-cell level in health and disease.
