期刊
DEVELOPMENTAL DYNAMICS
卷 -, 期 -, 页码 -出版社
WILEY
DOI: 10.1002/dvdy.556
关键词
enhancer; heart; injury; leptin; regeneration; zebrafish
By studying the heterogeneity of noncardiomyocytes in regenerating zebrafish hearts, we identified cellular types and factors involved in cardiac regeneration, revealing regenerative features of the heart.
BackgroundZebrafish possess a remarkable regenerative capacity, which is mediated by the induction of various genes upon injury. Injury-dependent transcription is governed by the tissue regeneration enhancer elements (TREEs). Here, we utilized leptin b (lepb), an injury-specific factor, and its TREE to dissect heterogeneity of noncardiomyocytes (CMs) in regenerating hearts. ResultsOur single-cell RNA sequencing (scRNA-seq) analysis demonstrated that the endothelium/endocardium(EC) is activated to induce distinct subpopulations upon injury. We demonstrated that lepb can be utilized as a regeneration-specific marker to subset injury-activated ECs. lepb(+) ECs robustly induce pro-regenerative factors, implicating lepb(+) ECs as a signaling center to interact with other cardiac cells. Our scRNA-seq analysis identified that lepb is also produced by subpopulation of epicardium (Epi) and epicardium-derived cells (EPDCs). To determine whether lepb labels injury-emerging non-CM cells, we tested the activity of lepb-linked regeneration enhancer (LEN) with chromatin accessibility profiles and transgenic lines. While nondetectable in uninjured hearts, LEN directs EC and Epi/EPDC expression upon injury. The endogenous LEN activity was assessed using LEN deletion lines, demonstrating that LEN deletion abolished injury-dependent expression of lepb, but not other nearby genes. ConclusionsOur integrative analyses identify regeneration-emerging cell-types and factors, leading to the discovery of regenerative features of hearts.
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