ArticleStem cells (Dayton, Ohio)2020
Canonical Wnt signaling promotes pacemaker cell specification of cardiac mesodermal cells derived from mouse and human embryonic stem cells.
Article in Stem cells (Dayton, Ohio), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- Molecular Mechanisms Underlying Pluripotency and Self-Renewal of Embryonic Stem Cells.International journal of molecular sciences · 2023Pooled it
- Review
- Article
- Hedgehog and Bmp signaling pathways play opposing roles during establishment of the cardiac inflow tract in zebrafish.Development (Cambridge, England) · 2026Article
- Pilot: Wnt signaling controlsmicroPublication biology · 2026Article
- Wnt/β-catenin signaling regulates cardiac Cx43 in a metabolic substrate-dependent manner.Journal of molecular and cellular cardiology plus · 2025Article
- Modelling neurocardiac physiology and diseases using human pluripotent stem cells: current progress and future prospects.The Journal of physiology · 2025Review
- Odz4 upregulates SAN-specific genes to promote differentiation into cardiac pacemaker-like cells.FEBS letters · 2025Article
- Bioprinting approaches in cardiac tissue engineering to reproduce blood-pumping heart function.iScience · 2025Review
- High Glucose Sensitizes Male and Female Rat Cardiomyocytes to Wnt/β-Catenin Signaling.Biomolecules · 2024Article
- Review
- Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes.Nature communications · 2024Article
- FunlncModel: integrating multi-omic features from upstream and downstream regulatory networks into a machine learning framework to identify functional lncRNAs.Briefings in bioinformatics · 2024Article
- A Foxf1-Wnt-Nr2f1 cascade promotes atrial cardiomyocyte differentiation in zebrafish.PLoS genetics · 2024Article
- A new paradigm for generating high-quality cardiac pacemaker cells from mouse pluripotent stem cells.Signal transduction and targeted therapy · 2024Article
- Engineered platforms for mimicking cardiac development and drug screening.Cellular and molecular life sciences : CMLS · 2024Review
- A Foxf1-Wnt-Nr2f1 cascade promotes atrial cardiomyocyte differentiation in zebrafish.bioRxiv : the preprint server for biology · 2024Article
- Heart rhythmFrontiers in cardiovascular medicine · 2024Article
- The sinoatrial node extracellular matrix promotes pacemaker phenotype and protects automaticity in engineered heart tissues from cyclic strain.Cell reports · 2023Article
- The role of c-Jun for beating cardiomycyte formation in prepared embryonic body.Stem cell research & therapy · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Cardiac differentiation of embryonic stem cells (ESCs) can give rise to de novo chamber cardiomyocytes and nodal pacemaker cells. Compared with our understanding of direct differentiation toward atrial and ventricular myocytes, the mechanisms for nodal pacemaker cell commitment are not well understood. Taking a cue from the prominence of canonical Wnt signaling during cardiac pacemaker tissue development in chick embryos, we asked if modulations of Wnt signaling influence cardiac progenitors to bifurcate to either chamber cardiomyocytes or pacemaker cells. Omitting an exogenous Wnt inhibitor, which is routinely added to maximize cardiac myocyte yield during differentiation of mouse and human ESCs, led to increased yield of spontaneously beating cardiomyocytes with action potential properties similar to those of native sinoatrial node pacemaker cells. The pacemaker phenotype was accompanied by enhanced expression of genes and gene products that mark nodal pacemaker cells such as Hcn4, Tbx18, Tbx3, and Shox2. Addition of exogenous Wnt3a ligand, which activates canonical Wnt/β-catenin signaling, increased the yield of pacemaker-like myocytes while reducing cTNT-positive pan-cardiac differentiation. Conversely, addition of inhibitors of Wnt/β-catenin signaling led to increased chamber myocyte lineage development at the expense of pacemaker cell specification. The positive impact of canonical Wnt signaling on nodal pacemaker cell differentiation was evidenced in direct differentiation of two human ESC lines and human induced pluripotent stem cells. Our data identify the Wnt/β-catenin pathway as a critical determinant of cardiac myocyte subtype commitment during ESC differentiation: endogenous Wnt signaling favors the pacemaker lineage, whereas its suppression promotes the chamber cardiomyocyte lineage.
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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.