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Publication : Single-cell dual-omics reveals the transcriptomic and epigenomic diversity of cardiac non-myocytes.

First Author  Wang L Year  2022
Journal  Cardiovasc Res Volume  118
Issue  6 Pages  1548-1563
PubMed ID  33839759 Mgi Jnum  J:356429
Mgi Id  MGI:7762521 Doi  10.1093/cvr/cvab134
Citation  Wang L, et al. (2022) Single-cell dual-omics reveals the transcriptomic and epigenomic diversity of cardiac non-myocytes. Cardiovasc Res 118(6):1548-1563
abstractText  AIMS: The precise cellular identity and molecular features of non-myocytes (non-CMs) in a mammalian heart at a single-cell level remain elusive. Depiction of epigenetic landscape with transcriptomic signatures using the latest single-cell multi-omics has the potential to unravel the molecular programs underlying the cellular diversity of cardiac non-myocytes. Here, we characterized the molecular and cellular features of cardiac non-CM populations in the adult murine heart at the single-cell level. METHODS AND RESULTS: Through single-cell dual omics analysis, we mapped the epigenetic landscapes, characterized the transcriptomic profiles and delineated the molecular signatures of cardiac non-CMs in the adult murine heart. Distinct cis-regulatory elements and trans-acting factors for the individual major non-CM cell types (endothelial cells, fibroblast, pericytes, and immune cells) were identified. In particular, unbiased sub-clustering and functional annotation of cardiac fibroblasts (FBs) revealed extensive FB heterogeneity and identified FB sub-types with functional states related to the cellular response to stimuli, cytoskeleton organization, and immune regulation, respectively. We further explored the function of marker genes Hsd11b1 and Gfpt2 that label major FB subpopulations and determined the distribution of Hsd11b1+ and Gfp2+ FBs in murine healthy and diseased hearts. CONCLUSIONS: In summary, we characterized the non-CM cellular identity at the transcriptome and epigenome levels using single-cell omics approaches and discovered previously unrecognized cardiac fibroblast subpopulations with unique functional states.
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