ArticleStem cell reports2015
SHOX2 overexpression favors differentiation of embryonic stem cells into cardiac pacemaker cells, improving biological pacing ability.
Article in Stem cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 135 citations in OpenAlex.
- Biomechanical Isolation is Required for Maintenance of the Cardiac Pacemaker Cell Fate.Research square · 2026Article
- Odz4 upregulates SAN-specific genes to promote differentiation into cardiac pacemaker-like cells.FEBS letters · 2025Article
- Review
- A new paradigm for generating high-quality cardiac pacemaker cells from mouse pluripotent stem cells.Signal transduction and targeted therapy · 2024Article
- Differentiation of Sinoatrial-like Cardiomyocytes as a Biological Pacemaker Model.International journal of molecular sciences · 2024Review
- State-of-the-Art Differentiation Protocols for Patient-Derived Cardiac Pacemaker Cells.International journal of molecular sciences · 2024Review
- The method of sinus node-like pacemaker cells from human induced pluripotent stem cells by BMP and Wnt signaling.Cell biology and toxicology · 2023Article
- Recent advances in pluripotent stem cell-derived cardiac organoids and heart-on-chip applications for studying anti-cancer drug-induced cardiotoxicity.Cell biology and toxicology · 2023Review
- Tbx5 overexpression in embryoid bodies increases TAK1 expression but does not enhance the differentiation of sinoatrial node cardiomyocytes.Biology open · 2023Article
- Local tissue mechanics control cardiac pacemaker cell embryonic patterning.Life science alliance · 2023Article
- Nr2f1a maintains atrialeLife · 2023Article
- Conversion of Unmodified Stem Cells to Pacemaker Cells by Overexpression of Key Developmental Genes.Cells · 2023Article
- Sinus node dysfunction: current understanding and future directions.American journal of physiology. Heart and circulatory physiology · 2023Review
- Disruption of the Gut Microbiota Confers Cisplatin Resistance in Epithelial Ovarian Cancer.Cancer research · 2022Article
- RA signaling pathway combined with Wnt signaling pathway regulates human-induced pluripotent stem cells (hiPSCs) differentiation to sinus node-like cells.Stem cell research & therapy · 2022Article
- Improved Generation of Human Induced Pluripotent Stem Cell-Derived Cardiac Pacemaker Cells Using Novel Differentiation Protocols.International journal of molecular sciences · 2022Article
- Cellular and Engineered Organoids for Cardiovascular Models.Circulation research · 2022Review
- A dualiScience · 2022Article
- Chemically defined and small molecules-based generation of sinoatrial node-like cells.Stem cell research & therapy · 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
1 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
When pluripotency factors are removed, embryonic stem cells (ESCs) undergo spontaneous differentiation, which, among other lineages, also gives rise to cardiac sublineages, including chamber cardiomyocytes and pacemaker cells. Such heterogeneity complicates the use of ESC-derived heart cells in therapeutic and diagnostic applications. We sought to direct ESCs to differentiate specifically into cardiac pacemaker cells by overexpressing a transcription factor critical for embryonic patterning of the native cardiac pacemaker (the sinoatrial node). Overexpression of SHOX2 during ESC differentiation upregulated the pacemaker gene program, resulting in enhanced automaticity in vitro and induced biological pacing upon transplantation in vivo. The accentuated automaticity is accompanied by temporally evolving changes in the effectors and regulators of Wnt signaling. Our findings provide a strategy for enriching the cardiac pacemaker cell population from ESCs.
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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 Socratic graph.