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
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE261428 | GEO | 2025/12/15
REPOSITORIES: GEO
Similar Datasets
Project description:Cardiac fibroblasts have a central role during the ventricular remodeling process associated to 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 have 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, and localize to the wounded myocardium. Combining epigenomic profiling with functional assays, we unveil important candidate regulators mediating their response to cardiac damage.
2025-12-15 | GSE267256 | GEO
Project description:Cardiac fibroblasts have a central role during the ventricular remodeling process associated to 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 have 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 wounded myocardium. Combining epigenomic profiling with functional assays, we unveil important candidate regulators mediating their response to cardiac damage. We show that the absence of CTHRC1, a top marker of this activated fibroblast subpopulation, results in pronounced lethality due to ventricular rupture within the first week post-myocardial infarction. Finally, we find evidence for the existence of similar mechanisms in a pig pre-clinical model of MI and establish a positive correlation between Cthrc1 levels and cardiac function after MI.
2020-09-29 | GSE132143 | GEO
Project description:Cardiac fibroblasts have a central role during the ventricular remodeling process associated to 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 have 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 wounded myocardium. Combining epigenomic profiling with functional assays, we unveil important candidate regulators mediating their response to cardiac damage. We show that the absence of CTHRC1, a top marker of this activated fibroblast subpopulation, results in pronounced lethality due to ventricular rupture within the first week post-myocardial infarction. Finally, we find evidence for the existence of similar mechanisms in a pig pre-clinical model of MI and establish a positive correlation between Cthrc1 levels and cardiac function after MI.
2020-09-29 | GSE132145 | GEO
Project description:Cardiac fibroblasts have a central role during the ventricular remodeling process associated to 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 have 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 wounded myocardium. Combining epigenomic profiling with functional assays, we unveil important candidate regulators mediating their response to cardiac damage. We show that the absence of CTHRC1, a top marker of this activated fibroblast subpopulation, results in pronounced lethality due to ventricular rupture within the first week post-myocardial infarction. Finally, we find evidence for the existence of similar mechanisms in a pig pre-clinical model of MI and establish a positive correlation between Cthrc1 levels and cardiac function after MI.
2020-09-29 | GSE132144 | GEO
Project description:Cardiac fibroblasts have a central role during the ventricular remodeling process associated to 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 have 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, and localize to the wounded myocardium. Combining epigenomic profiling with functional assays, we unveil important candidate regulators mediating their response to cardiac damage.
2025-12-15 | GSE265828 | GEO
Project description:Transcriptome analysis of RNA samples from cultured cardiac fibroblasts Excessive extracellular matrix accumulation in the myocardium is a poor prognostic factor for reduced left ventricular function. It is known that improvement of hemodynamic loading improves myocardial fibrosis, but in vitro models of the pathogenesis have not been established, and the potential mechanism of fibrosis resolution have not clarified. We reproduced normal myocardium, fibrotic myocardium following hemodynamic loading and myocardium with improved fibrosis following hemodynamic loading reduction in vitro. Fibroblasts were activated to αSMA+ fibroblasts on myocardium following hemodynamic loading. On myocardium following hemodynamic loading reduction, they were deactivated to αSMA- fibroblasts, and their phenotype changed to fibrinolytic cells expressing MMP2 and MMP9. Comprehensive gene expression analysis of fibroblasts in each in vitro model revealed that Selenbp1 is one of the genes responsible for regulation of phenotypic changes in fibroblasts. In vitro, knockdown of Selenbp1 using RNA interference enhanced fibroblast activation and inhibited conversion to the fibrinolytic form. In vivo, knockdown of Selenbp1 caused structural changes in the left ventricle associated with progressive tissue fibrosis and left ventricular diastolic failure. Selenbp1 is involved in the regulation of fibroblast phenotype and was found to be one of the major molecules regulating collagen turnover in cardiac fibrosis.
2025-10-03 | GSE214665 | GEO
Project description:Cardiac fibroblasts are critical to proper heart function through multiple interactions with the myocardial compartment. Loosely defined based on their mesenchymal origin, capacity to adhere to plastic and to secrete extracellular matrix, cardiac fibroblasts have been largely neglected due to heterogeneity and lack of proper markers. Objective: To identify genes uniquely expressed in the cardiac fibroblast pool, we performed an unbiased comparative analysis between cardiac and tail fibroblasts, and tracked cardiac fibroblasts after injury to determine their contribution to myocardial regeneration. Methods and Results: High-throughput cell surface and intracellular profiling identified homogeneously expressed MSC markers in cardiac fibroblasts, as well as a surprising number of cardiogenic markers, some expressed at higher levels than in cardiomyocytes. Genetically marked fibroblasts contributed to interstitial but not cardiomyocyte compartments in infarcted hearts. Conclusions: The core transcriptional identity of cardiac fibroblasts reflects their embryological origin, provoking novel interpretations for studies on more specialized cardiac progenitors, and offering a novel perspective for reinterpreting cardiac regenerative therapies 3 biological replicates plated over 5 days after isolation pooled out of 2 animals were used for both tail and heart fibroblasts (6 total samples analysed)
2014-05-20 | E-GEOD-50531 | biostudies-arrayexpress
Project description:Cardiac fibroblasts are critical to proper heart function through multiple interactions with the myocardial compartment. Loosely defined based on their mesenchymal origin, capacity to adhere to plastic and to secrete extracellular matrix, cardiac fibroblasts have been largely neglected due to heterogeneity and lack of proper markers. Objective: To identify genes uniquely expressed in the cardiac fibroblast pool, we performed an unbiased comparative analysis between cardiac and tail fibroblasts, and tracked cardiac fibroblasts after injury to determine their contribution to myocardial regeneration. Methods and Results: High-throughput cell surface and intracellular profiling identified homogeneously expressed MSC markers in cardiac fibroblasts, as well as a surprising number of cardiogenic markers, some expressed at higher levels than in cardiomyocytes. Genetically marked fibroblasts contributed to interstitial but not cardiomyocyte compartments in infarcted hearts. Conclusions: The core transcriptional identity of cardiac fibroblasts reflects their embryological origin, provoking novel interpretations for studies on more specialized cardiac progenitors, and offering a novel perspective for reinterpreting cardiac regenerative therapies
2014-05-20 | GSE50531 | GEO
Project description:Myocardial damage caused for example by cardiac ischemia leads to ventricular volume overload resulting in increased stretch of the remaining myocardium. In adult mammals, these changes trigger an adaptive cardiomyocyte hypertrophic response which, if the damage is extensive, will ultimately lead to pathological hypertrophy and heart failure. Conversely, in response to extensive myocardial damage, cardiomyocytes in the adult zebrafish heart and neonatal mice proliferate and completely regenerate the damaged myocardium. We therefore hypothesized that in adult zebrafish, changes in mechanical loading due to myocardial damage may act as a trigger to induce cardiac regeneration. Based, on this notion we sought to identify mechanosensors which could be involved in detecting changes in mechanical loading and triggering regeneration. Here we show using a combination of knockout animals, RNAseq and in vitro assays that the mechanosensitive ion channel Trpc6a is required by cardiomyocytes for successful cardiac regeneration in adult zebrafish. Furthermore, using a cyclic cell stretch assay, we have determined that Trpc6a induces the expression of components of the AP1 transcription complex in response to mechanical stretch. Our data highlights how changes in mechanical forces due to myocardial damage can be detected by mechanosensors which in turn can trigger cardiac regeneration.
2023-12-20 | E-MTAB-13603 | biostudies-arrayexpress
Project description:This a model from the article:
Electrophysiological modeling of fibroblasts and their interaction with myocytes.
Sachse FB, Moreno AP, Abildskov JA. Ann Biomed Eng.
year volume page 17999190
,
Abstract:
Experimental studies have shown that cardiac fibroblasts are electrically inexcitable, but can contribute to electrophysiology of myocardium in various manners. The aim of this computational study was to give insights in the electrophysiological role of fibroblasts and their interaction with myocytes. We developed a mathematical model of fibroblasts based on data from whole-cell patch clamp and polymerase chain reaction (PCR) studies. The fibroblast model was applied together with models of ventricular myocytes to assess effects of heterogeneous intercellular electrical coupling. We investigated the modulation of action potentials of a single myocyte varying the number of coupled fibroblasts and intercellular resistance. Coupling to fibroblasts had only a minor impact on the myocyte's resting and peak transmembrane voltage, but led to significant changes of action potential duration and upstroke velocity. We examined the impact of fibroblasts on conduction in one-dimensional strands of myocytes. Coupled fibroblasts reduced conduction and upstroke velocity. We studied electrical bridging between ventricular myocytes via fibroblast insets for various coupling resistors. The simulations showed significant conduction delays up to 20.3 ms. In summary, the simulations support strongly the hypothesis that coupling of fibroblasts to myocytes modulates electrophysiology of cardiac cells and tissues.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
sachse, moreno, abildskov.(2008) - version05
The original CellML model was created by:
Lloyd, Catherine, May
c.lloyd@auckland.ac.nz
The University of Auckland
Auckland Bioengineering Institute
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2005-01-01 | MODEL7914759868 | BioModels