Single-Cell RNA Sequencing Unveils Unique Transcriptomic Signatures of Organ-Specific Endothelial Cells. Circulation 2020 Nov 10;142(19):1848-1862
Date
09/16/2020Pubmed ID
32929989Pubmed Central ID
PMC7658053DOI
10.1161/CIRCULATIONAHA.119.041433Scopus ID
2-s2.0-85095970633 (requires institutional sign-in at Scopus site) 135 CitationsAbstract
BACKGROUND: Endothelial cells (ECs) display considerable functional heterogeneity depending on the vessel and tissue in which they are located. Whereas these functional differences are presumably imprinted in the transcriptome, the pathways and networks that sustain EC heterogeneity have not been fully delineated.
METHODS: To investigate the transcriptomic basis of EC specificity, we analyzed single-cell RNA sequencing data from tissue-specific mouse ECs generated by the Tabula Muris consortium. We used a number of bioinformatics tools to uncover markers and sources of EC heterogeneity from single-cell RNA sequencing data.
RESULTS: We found a strong correlation between tissue-specific EC transcriptomic measurements generated by either single-cell RNA sequencing or bulk RNA sequencing, thus validating the approach. Using a graph-based clustering algorithm, we found that certain tissue-specific ECs cluster strongly by tissue (eg, liver, brain), whereas others (ie, adipose, heart) have considerable transcriptomic overlap with ECs from other tissues. We identified novel markers of tissue-specific ECs and signaling pathways that may be involved in maintaining their identity. Sex was a considerable source of heterogeneity in the endothelial transcriptome and we discovered Lars2 to be a gene that is highly enriched in ECs from male mice. We found that markers of heart and lung ECs in mice were conserved in human fetal heart and lung ECs. We identified potential angiocrine interactions between tissue-specific ECs and other cell types by analyzing ligand and receptor expression patterns.
CONCLUSIONS: We used single-cell RNA sequencing data generated by the Tabula Muris consortium to uncover transcriptional networks that maintain tissue-specific EC identity and to identify novel angiocrine and functional relationships between tissue-specific ECs.
Author List
Paik DT, Tian L, Williams IM, Rhee S, Zhang H, Liu C, Mishra R, Wu SM, Red-Horse K, Wu JCAuthor
Chun Liu PhD Assistant Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsDatabases, Nucleic Acid
Endothelial Cells
Female
Male
Mice
Organ Specificity
Sex Characteristics
Single-Cell Analysis
Transcriptome
