ArticleThe Journal of clinical investigation2015
Transcription factor ISL1 is essential for pacemaker development and function.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.
What it found
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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
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.
- 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
- Biomechanical Isolation is Required for Maintenance of the Cardiac Pacemaker Cell Fate.Research square · 2026Article
- The cardiac conduction system: development, function and therapeutic targets.Nature reviews. Cardiology · 2026Review
- PITX2 dosage-dependent changes in pacemaker cell state underlie sinus node dysfunction and atrial arrhythmias.Nature communications · 2025Article
- Genetic knockout suggests Isl1 enhancer redundancy in mouse hindlimb development.Developmental biology · 2025Article
- Review
- A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival.Nature communications · 2024Article
- Molecular Regulation of Cardiac Conduction System Development.Current cardiology reports · 2024Review
- Transcriptional regulation of the postnatal cardiac conduction system heterogeneity.Nature communications · 2024Article
- TBX3 transfection and nodal signal pathway inhibition promote differentiation of adipose mesenchymal stem cell to cardiac pacemaker-like cells.Stem cell research & therapy · 2024Article
- TAD boundary deletion causes PITX2-related cardiac electrical and structural defects.Nature communications · 2024Article
- Article
- Development of the Cardiac Conduction System.Advances in experimental medicine and biology · 2024Article
- Cardiac Development at a Single-Cell Resolution.Advances in experimental medicine and biology · 2024Article
- The method of sinus node-like pacemaker cells from human induced pluripotent stem cells by BMP and Wnt signaling.Cell biology and toxicology · 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
- Harnessing cell reprogramming for cardiac biological pacing.Journal of biomedical science · 2023Review
- Local tissue mechanics control cardiac pacemaker cell embryonic patterning.Life science alliance · 2023Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 4 institutions in 2 countries.
Funding
Abstract
The sinoatrial node (SAN) maintains a rhythmic heartbeat; therefore, a better understanding of factors that drive SAN development and function is crucial to generation of potential therapies, such as biological pacemakers, for sinus arrhythmias. Here, we determined that the LIM homeodomain transcription factor ISL1 plays a key role in survival, proliferation, and function of pacemaker cells throughout development. Analysis of several Isl1 mutant mouse lines, including animals harboring an SAN-specific Isl1 deletion, revealed that ISL1 within SAN is a requirement for early embryonic viability. RNA-sequencing (RNA-seq) analyses of FACS-purified cells from ISL1-deficient SANs revealed that a number of genes critical for SAN function, including those encoding transcription factors and ion channels, were downstream of ISL1. Chromatin immunoprecipitation assays performed with anti-ISL1 antibodies and chromatin extracts from FACS-purified SAN cells demonstrated that ISL1 directly binds genomic regions within several genes required for normal pacemaker function, including subunits of the L-type calcium channel, Ank2, and Tbx3. Other genes implicated in abnormal heart rhythm in humans were also direct ISL1 targets. Together, our results demonstrate that ISL1 regulates approximately one-third of SAN-specific genes, indicate that a combination of ISL1 and other SAN transcription factors could be utilized to generate pacemaker cells, and suggest ISL1 mutations may underlie sick sinus syndrome.
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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.