Single-cell RNA-seq analysis reveals the crucial role of Collagen Triplex Helix Repeat Containing 1 (CTHRC1) cardiac fibroblasts for ventricular remodeling after myocardial infarction
Juan P. Romero,
Silvia C Hernandez,
Patxi San Martin-Uriz,
Juan José Gavira,
Xabier Martinez de Morentin,
Posted 20 May 2019
bioRxiv DOI: 10.1101/643130
Posted 20 May 2019
Cardiac fibroblasts have a central role during the ventricular remodeling process associated with different types of cardiac injury. Recent studies have shown that fibroblasts do not respond homogeneously to heart damage, suggesting that the adult myocardium may contain specialized fibroblast subgroups with specific functions. Due to the limited set of bona fide fibroblast markers, a proper characterization of fibroblast population dynamics in response to cardiac damage is still missing. Using single-cell RNA-seq, we identified and characterized a fibroblast subpopulation that emerges in response to myocardial infarction (MI) in a murine model. These activated fibroblasts exhibit a clear pro-fibrotic signature, express high levels of the hormone CTHRC1 and of the immunomodulatory co-receptor CD200 and localize to the injured myocardium. Combining epigenomic profiling with functional assays, we show Sox9 and the non-canonical TGF-β signaling as important regulators mediating their response to cardiac damage. We show that the absence of CTHRC1, in this activated fibroblast subpopulation, results in pronounced lethality due to ventricular rupture in a mouse model of myocardial infarction. Finally, we find evidence for the existence of similar mechanisms in a pig preclinical model of MI and establish a correlation between CTHRC1 levels and cardiac function after MI.
- Downloaded 1,251 times
- Download rankings, all-time:
- Site-wide: 21,031
- In cell biology: 675
- Year to date:
- Site-wide: 56,350
- Since beginning of last month:
- Site-wide: 125,159
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!