GSE185345
Defining the Transcriptional and Epigenetic Basis of Organotypic Endothelial Diversity in the Developing and Adult Mouse
The transport of gases, nutrients, metabolites and cells -  a prerequisite for proper organogenesis and tissue homeostasis - requires a functional circulatory system consisting of arteries and veins, separated by intervening capillary networks. Despite their shared origin and some common functions, endothelial cells (ECs), which line every blood vessel, display profound structural and functional heterogeneity unique to the organ and tissue that they reside in. The diversity of phenotypes that ECs can adopt suggest substantial plasticity and indicates that heterogeneity is a core endothelial property that allows ECs to fulfill their multiple tasks. While the anatomical heterogeneity of blood vessels across different organs has been appreciated for centuries, the molecular basis of the variation within the vertebrate vascular tree is poorly understood.   To decipher the transcriptional and epigenetic basis of endothelial heterogeneity across organs, and to determine how ECs mature during development, we surveyed the transcriptional and accessible chromatin landscape of ECs from the brain, retina, heart, liver, lung, and kidney of E12.5, P6, and adult mice. Through analysis of differential gene expression signatures, as well as chromatin accessibility, we have identified unique transcripts, as well as regulatory regions, that define each organ bed and developmental time point. Additionally, through single cell RNA-seq profiling of the embryonic and adult mouse we have determined that the endothelium of a single organ - in this case the brain - uses a diverse set of gene regulatory networks to mature and create a functional blood brain barrier. Overall design: Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) and RNA-seq of endothelial cells (Ecs) or input nuclei of trunk, heart and brain at embryonic day 12.5 and brain, retina, heart, lung, liver and kidney at postnatal day 6 and adult (2 month old) mice; single cell RNA-seq of ECs at embryonic day 9.5, 12.5, 16.5, postnatal day 8 and adult (2 month old) mouse brain.