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bioRxiv · 10.1101/2021.05.12.443777

Single-cell epigenomic tracing of lifelong endothelial cell plasticity across mouse organs

Yu, X.·Liu, Y.·Liu, X.·Xiong, H.·He, A.
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Abstract

Endothelial cells (ECs) across ages and tissues are highly heterogeneous in developmental origins, structures, functions, and cellular plasticity. Here, we applied CoBATCH for single-cell epigenomic tracing of dynamic EC lineage histories in five mouse organs from development to ageing. Our analyses showed that epigenomic memory reflects both developmental origins and tissue-restricted specialization of EC sublineages but with varying time lengths across organs. To gain insights into cellular plasticity of ECs, we identified bivalent chromatin occupancy of otherwise mutually exclusive EC- (ERG) and mesenchymal-specific (TWIST1/SNAI1) transcription factors promoting endothelial-to-mesenchymal transition. We further revealed that pseudotime trajectories by histone modifications H3K36me3 and H3K27ac faithfully recapitulate short- and long-range EC fate change over senescence, respectively. Together, our data provide a unique exploration of chromatin-level cell fate regulation of organotypic EC lineages across the lifespan. One-Sentence SummarySingle-cell chromatin binding is examined for tracing endothelial cell lineages in mouse organs across the lifespan.

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Yu, X., Liu, Y., Liu, X., Xiong, H., He, A.. 2021-05-13. Single-cell epigenomic tracing of lifelong endothelial cell plasticity across mouse organs. https://doi.org/10.1101/2021.05.12.443777

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