PXD069415

PXD069415 is an original dataset announced via ProteomeXchange.

Title	Grhl3 Downregulation Drives Extracellular Matrix Adaptation to Cell Fate Commitment from Fibroblasts to Induced Cardiomyocytes
Description	Myocardial infarction (MI) remains as one of the leading causes of heart failure. Following MI, excessive extracellular matrix (ECM) deposition forms a rigid fibrotic scar, leading to pathological remodeling and functional adaptation, which drives heart failure and the onset of arrhythmia. Changes of myocardial ECM have been reported to diversely regulate tissue repair, supporting the notion that remodeling ECM proteins would be a critical strategy to enhance heart regeneration. Direct cardiac reprogramming holds promising translational potential for heart regeneration by converting fibroblasts directly into induced cardiomyocytes (iCMs), and the field is now starting to unveil how the ECM and cellular microenvironment affects iCM generation. Through ECM related pathway activity analysis, we observed that integrin related pathways were dysregulated in iCMs, and identified integrin alpha-8 (Itga8) as the critical ECM receptor that suppresses iCMs reprogramming. A loss-of-function screen showed that grainyhead-like protein 3 homolog (Grhl3) was a key regulator of integrins, including Itga8, which impairs iCM generation. Integrative analysis using RNA sequencing and CUT&Tag profiling histone 3 lysine 27 acetylation revealed that loss of Grhl3 remodels ECM composition to a more CM-like state that enhances iCM conversion. In addition, Grhl3 deficiency further enhanced functional improvement and reduced scar size after myocardial injury. Our work highlights the indispensable roles of ECM in regulating iCM conversion.
HostingRepository	iProX
AnnounceDate	2025-10-14
AnnouncementXML	Submission_2026-01-05_22:52:55.607.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xin Wu
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-13 20:24:33	ID requested
⏵ 1	2026-01-05 22:52:56	announced

Dataset with its publication pending

submitter keyword: direct reprogramming, heart regeneration, extracellular matrix remodeling, GRHL3

Li Wang
contact affiliation	Wuhan University
contact email	liwang2020@whu.edu.cn
lab head
Xin Wu
contact affiliation	Wuhan University
contact email	wuxin_9924@whu.edu.cn
dataset submitter

iProX dataset URI