ArticleScientific reports2020
NOTCH1 is critical for fibroblast-mediated induction of cardiomyocyte specialization into ventricular conduction system-like cells in vitro.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Contactin-2 mitigates heart failure and cardiac remodeling via regulation of NUPR1 and ferroptosis.Biology direct · 2026Article
- The cardiac conduction system: development, function and therapeutic targets.Nature reviews. Cardiology · 2026Review
- End-stage valvular heart disease requiring heart transplantation: risk profile, surgical modifiers, and myocardial pathology.BMC cardiovascular disorders · 2026Article
- Article
- Cardiac Development, Cellular Composition and Function: From Regulatory Mechanisms to Applications.Cells · 2025Review
- Analysis of endogenous NOTCH1 from POFUT1 S162L patient fibroblasts reveals the importance of the O-fucose modification on EGF12 in human development.Glycobiology · 2024Article
- Adriamycin induces cardiac fibrosis in mice via PRMT5-mediated cardiac fibroblast activation.Acta pharmacologica Sinica · 2023Article
- Multicellular 3D Models for the Study of Cardiac Fibrosis.International journal of molecular sciences · 2022Review
- The Roles of Cardiac Fibroblasts and Endothelial Cells in Myocarditis.Frontiers in cardiovascular medicine · 2022Review
- Pacemaker translocations and power laws in 2D stem cell-derived cardiomyocyte cultures.PloS one · 2022Article
- Bioengineering Systems for Modulating Notch Signaling in Cardiovascular Development, Disease, and Regeneration.Journal of cardiovascular development and disease · 2021Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cardiac fibroblasts are present throughout the myocardium and are enriched in the microenvironment surrounding the ventricular conduction system (VCS). Several forms of arrhythmias are linked to VCS abnormalities, but it is still unclear whether VCS malformations are cardiomyocyte autonomous or could be linked to crosstalk between different cell types. We reasoned that fibroblasts influence cardiomyocyte specialization in VCS cells. We developed 2D and 3D culture models of neonatal rat cardiac cells to assess the influence of cardiac fibroblasts on cardiomyocytes. Cardiomyocytes adjacent to cardiac fibroblasts showed a two-fold increase in expression of VCS markers (NAV1.5 and CONTACTIN 2) and calcium transient duration, displaying a Purkinje-like profile. Fibroblast-conditioned media (fCM) was sufficient to activate VCS-related genes (Irx3, Scn5a, Connexin 40) and to induce action potential prolongation, a hallmark of Purkinge phenotype. fCM-mediated response seemed to be spatially-dependent as cardiomyocyte organoids treated with fCM had increased expression of connexin 40 and NAV1.5 primarily on its outer surface. Finally, NOTCH1 activation in both cardiomyocytes and fibroblasts was required for connexin 40 up-regulation (a proxy of VCS phenotype). Altogether, we provide evidence that cardiac fibroblasts influence cardiomyocyte specialization into VCS-like cells via NOTCH1 signaling in vitro.
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