RT Journal Article
T1 Single-Cell RNA Sequencing Analysis Reveals a Crucial Role for CTHRC1 (Collagen Triple Helix Repeat Containing 1) Cardiac Fibroblasts After Myocardial Infarction.
A1 Ruiz-Villalba, Adrián
A1 Romero, Juan P
A1 Hernández, Silvia C
A1 Vilas-Zornoza, Amaia
A1 Fortelny, Nikolaus
A1 Castro-Labrador, Laura
A1 San Martin-Uriz, Patxi
A1 Lorenzo-Vivas, Erika
A1 García-Olloqui, Paula
A1 Palacio, Marcel
A1 Gavira, Juan José
A1 Bastarrika, Gorka
A1 Janssens, Stefan
A1 Wu, Ming
A1 Iglesias, Elena
A1 Abizanda, Gloria
A1 de Morentin, Xabier Martinez
A1 Lasaga, Miren
A1 Planell, Nuria
A1 Bock, Christoph
A1 Alignani, Diego
A1 Medal, Gema
A1 Prudovsky, Igor
A1 Jin, Yong-Ri
A1 Ryzhov, Sergey
A1 Yin, Haifeng
A1 Pelacho, Beatriz
A1 Gomez-Cabrero, David
A1 Lindner, Volkhard
A1 Lara-Astiaso, David
A1 Prósper, Felipe
K1 fibroblasts
K1 myocardial infarction
K1 sequence analysis, RNA
AB Cardiac fibroblasts (CFs) have a central role in the ventricular remodeling process associated with different types of fibrosis. Recent studies have shown that fibroblasts do not respond homogeneously to heart injury. Because of the limited set of bona fide fibroblast markers, a proper characterization of fibroblast population heterogeneity in response to cardiac damage is lacking. The purpose of this study was to define CF heterogeneity during ventricular remodeling and the underlying mechanisms that regulate CF function. Collagen1α1-GFP (green fluorescent protein)-positive CFs were characterized after myocardial infarction (MI) by single-cell and bulk RNA sequencing, assay for transposase-accessible chromatin sequencing, and functional assays. Swine and patient samples were studied using bulk RNA sequencing. We identified and characterized a unique CF subpopulation that emerges after MI in mice. These activated fibroblasts exhibit a clear profibrotic signature, express high levels of Cthrc1 (collagen triple helix repeat containing 1), and localize into the scar. Noncanonical transforming growth factor-β signaling and different transcription factors including SOX9 are important regulators mediating their response to cardiac injury. Absence of CTHRC1 results in pronounced lethality attributable to ventricular rupture. A population of CFs with a similar transcriptome was identified in a swine model of MI and in heart tissue from patients with MI and dilated cardiomyopathy. We report CF heterogeneity and their dynamics during the course of MI and redefine the CFs that respond to cardiac injury and participate in myocardial remodeling. Our study identifies CTHRC1 as a novel regulator of the healing scar process and a target for future translational studies.
YR 2020
FD 2020-09-25
LK http://hdl.handle.net/10668/16309
UL http://hdl.handle.net/10668/16309
LA en
DS RISalud
RD Apr 9, 2025