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Status Public on Nov 07, 2025

Title Single-cell analysis reveals the epigenetic remodeling and key effectors of non-cardiomyocytes during heart regeneration.

Organism Mus musculus

Experiment type Genome binding/occupancy profiling by high throughput sequencing

Summary The restricted regenerative potential of adult hearts poses a significant barrier to effective repair following injury. In contrast to numerous vertebrates, mammalian hearts exhibit only transient neonatal renewal capacity during the initial days of life. Beyond cardiomyocytes, understanding the diverse compositions of non-cardiomyocytes (non-CMs) is imperative for maintaining heart microenvironment homeostasis during neonatal heart regeneration. Here, we conducted single-cell ATAC sequencing (scATAC-seq) on neonatal hearts at varying time points post-apical resection to profile the epigenetic landscape. Intriguingly, fibroblasts and endothelial cells, as the most abundant populations in the heart, exhibited the most dynamic chromatin remodeling as the heart loses its regenerative potential. Our application of scATAC-seq unveiled key regulatory elements such as Cebpd in fibroblast activation and proliferation, while highlighting the essential role of AP-1 in endothelial cell angiogenesis, migration, and proliferation. Additionally, we uncovered active engagement of regulatory elements identified by non-CMs in regulating the behavior of cardiomyocytes, inhibition of which impaired cardiac function post-injury. Collectively, our study delineates the cellular identity of non-CMs at the epigenome level using single-cell approaches, offering insights into cell-type-targeted interventions for heart regeneration.

Overall design The epigenomic landscape of non-CMs of 7 and 14-day old mice in response to injury.

Contributor(s) Chen Z, Nie Y, Huang L

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Submission date Jun 05, 2024

Last update date Nov 07, 2025

Contact name Yage Nie

E-mail(s) nieyg5@mail2.sysu.edu.cn

Organization name Sun Yat-sen University

Street address No.74 Zhongshan Rd.2, Guangzhou

City Guangzhou

ZIP/Postal code 510000

Country China

Platforms (1)

Samples (6)

Relations

BioProject PRJNA1120444

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SOFT formatted family file(s) SOFT

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Series Matrix File(s) TXT

Supplementary file Size Download File type/resource

GSE269164_RAW.tar 7.5 Gb (http) (custom) TAR (of TBI, TSV)

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Raw data are available in SRA