ArticleStem cells (Dayton, Ohio)2015
Direct nkx2-5 transcriptional repression of isl1 controls cardiomyocyte subtype identity.
Article in Stem cells (Dayton, Ohio), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 2 syntheses or guidelines pooled it, 106 citations in OpenAlex.
- Pooled it
- Correlations between ISL1 rs1017 polymorphism and congenital heart disease risk: A PRISMA-compliant meta-analysis.Medicine · 2020Pooled it
- Nr2f1a and Isl1 repress acquisition of epicardial identity in venous atrial cardiomyocytes.Development (Cambridge, England) · 2026Article
- Benchmarking and optimizing Perturb-seq in differentiating human pluripotent stem cells.Stem cell reports · 2025Article
- From Petri Dish to Primitive Heart: How IVF Alters Early Cardiac Gene Networks and Epigenetic Landscapes.Biomedicines · 2025Review
- The method of sinus node-like pacemaker cells from human induced pluripotent stem cells by BMP and Wnt signaling.Cell biology and toxicology · 2023Article
- An Anterior Second Heart Field Enhancer Regulates the Gene Regulatory Network of the Cardiac Outflow Tract.Circulation · 2023Article
- The multi-lineage transcription factor ISL1 controls cardiomyocyte cell fate through interaction with NKX2.5.Stem cell reports · 2023Article
- Advances and Prospects in Understanding Vertebrate Cardiac Conduction System, Pacemaker Cell, and Cardiac Muscle Development: Toward Novel Biological Therapies.Muscles (Basel, Switzerland) · 2023Review
- The second heart field: the first 20 years.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Review
- Use of Frogs as a Model to Study the Etiology of HLHS.Journal of cardiovascular development and disease · 2023Article
- Nkx2.5: a crucial regulator of cardiac development, regeneration and diseases.Frontiers in cardiovascular medicine · 2023Review
- Tissue-specific multi-omics analysis of atrial fibrillation.Nature communications · 2022Article
- Comprehensive transcriptome-wide analysis of spliceopathy correction of myotonic dystrophy using CRISPR-Cas9 in iPSCs-derived cardiomyocytes.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Spatiotemporal expression of long noncoding RNARNA biology · 2021Article
- A BMP4-p38 MAPK signaling axis controls ISL1 protein stability and activity during cardiogenesis.Stem cell reports · 2021Article
- Spotlight on Isl1: A Key Player in Cardiovascular Development and Diseases.Frontiers in cell and developmental biology · 2021Review
- Bioengineering the Cardiac Conduction System: Advances in Cellular, Gene, and Tissue Engineering for Heart Rhythm Regeneration.Frontiers in bioengineering and biotechnology · 2021Review
- Molecular Signatures and Networks of Cardiomyocyte Differentiation in Humans and Mice.Molecular therapy. Nucleic acids · 2020Article
- Enrichment differentiation of human induced pluripotent stem cells into sinoatrial node-like cells by combined modulation of BMP, FGF, and RA signaling pathways.Stem cell research & therapy · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During cardiogenesis, most myocytes arise from cardiac progenitors expressing the transcription factors Isl1 and Nkx2-5. Here, we show that a direct repression of Isl1 by Nkx2-5 is necessary for proper development of the ventricular myocardial lineage. Overexpression of Nkx2-5 in mouse embryonic stem cells (ESCs) delayed specification of cardiac progenitors and inhibited expression of Isl1 and its downstream targets in Isl1(+) precursors. Embryos deficient for Nkx2-5 in the Isl1(+) lineage failed to downregulate Isl1 protein in cardiomyocytes of the heart tube. We demonstrated that Nkx2-5 directly binds to an Isl1 enhancer and represses Isl1 transcriptional activity. Furthermore, we showed that overexpression of Isl1 does not prevent cardiac differentiation of ESCs and in Xenopus laevis embryos. Instead, it leads to enhanced specification of cardiac progenitors, earlier cardiac differentiation, and increased cardiomyocyte number. Functional and molecular characterization of Isl1-overexpressing cardiomyocytes revealed higher beating frequencies in both ESC-derived contracting areas and Xenopus Isl1-gain-of-function hearts, which associated with upregulation of nodal-specific genes and downregulation of transcripts of working myocardium. Immunocytochemistry of cardiomyocyte lineage-specific markers demonstrated a reduction of ventricular cells and an increase of cells expressing the pacemaker channel Hcn4. Finally, optical action potential imaging of single cardiomyocytes combined with pharmacological approaches proved that Isl1 overexpression in ESCs resulted in normally electrophysiologically functional cells, highly enriched in the nodal subtype at the expense of the ventricular lineage. Our findings provide an Isl1/Nkx2-5-mediated mechanism that coordinately regulates the specification of cardiac progenitors toward the different myocardial lineages and ensures proper acquisition of myocyte subtype identity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.