Abstract 642: Single-Cell RNA-seq Unveils Unique Transcriptomic Signatures of Organ-Specific Endothelial Cells

Abstract

Endothelial cells (ECs) display considerable functional heterogeneity depending on the vessel and tissue in which they are located. While these functional differences are presumably imprinted in the transcriptome, the pathways and networks which sustain EC heterogeneity have not been fully delineated. To investigate the transcriptional control of EC specification, we analyzed single-cell RNA-sequencing (scRNA-Seq) data from tissue-specific mouse ECs generated by the Tabula Muris consortium. We found a strong correlation between tissue-specific EC transcriptomic measurements generated by either scRNA-Seq or bulk RNA-Seq, thus validating the approach. Using a graph-based clustering algorithm, we found that certain tissue-specific ECs cluster strongly by tissue (e.g. liver, brain) whereas others (i.e. adipose, heart) have considerable transcriptional overlap with ECs from other tissue. Using gene set enrichment analysis, we identified novel markers of tissue-specific ECs and signaling pathways that may be involved in maintaining their identity. By performing pseudotime trajectory analysis, we found that ECs from endoderm-derived tissues appear to be more developmentally immature when compared with the highly specialized ECs of ectoderm-derived tissues such as brain. In addition, we compared these data from mouse with human fetal heart scRNA-seq data for interspecies correlation in organ-specific EC gene expression. Finally, we identified potential angiocrine interactions between tissue-specific ECs and other cell types by analyzing ligand and receptor expression patterns. In summary, we have utilized scRNA-Seq to uncover transcriptional networks which maintain EC identity and identify novel developmental and angiocrine relationships between tissue-specific ECs.