A cross-study transcriptional patient map of heart failure defines conserved multicellular coordination in cardiac remodeling

Jan D. Lanzer, Ricardo O. Ramirez Flores, José Liñares Blanco, Marco Steier, Ashraf Y. Rangrez, Norbert Frey and Julio Saez-Rodriguez ()
Additional contact information
Jan D. Lanzer: Institute for Computational Biomedicine
Ricardo O. Ramirez Flores: Institute for Computational Biomedicine
José Liñares Blanco: European Bioinformatics Institute (EMBL-EBI)
Marco Steier: partner site Heidelberg/Mannheim
Ashraf Y. Rangrez: partner site Heidelberg/Mannheim
Norbert Frey: partner site Heidelberg/Mannheim
Julio Saez-Rodriguez: Institute for Computational Biomedicine

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: Abstract Impaired cardiac function in heart failure (HF) involves tissue remodeling through multicellular coordination. Although individual bulk and single-nucleus transcriptomics studies have offered insights, they have not been integrated to study conserved tissue-wide responses, limiting understanding of multicellular processes in cardiac remodeling necessary for therapeutic translation. Here, we integrate 25 studies of bulk and single-nucleus transcriptomics, spanning 1524 individuals, to define consensus multicellular programs associated with HF. These programs reveal conserved fibrotic, inflammatory, metabolic, and hypertrophic processes, with fibroblast activity consistently predicting cardiomyocyte stress. Our integration revealed that multicellular programs in HF are largely independent of tissue composition, and that fibroblast activation reflects a broad phenotypic shift rather than solely the emergence of discrete subtypes. Projecting external datasets onto these programs showed that clinical recovery aligns with reversion of disease-associated programs. This integrative analysis across studies establishes a public reference for the exploration of multicellular coordination in HF.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-025-62219-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62219-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-62219-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().