ArticleCirculation research2011
Small-molecule inhibitors of the Wnt pathway potently promote cardiomyocytes from human embryonic stem cell-derived mesoderm.
Article in Circulation research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
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Who cites it
114 citing papers in PubMed, 243 citations in OpenAlex.
- MicroRNA expression, target genes, and signaling pathways in infants with a ventricular septal defect.Molecular and cellular biochemistry · 2018Trial
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- Advances in Internal Organogenesis: Differentiation and Morphogenesis of Human Ventral Cavity Organs.Stem cell reviews and reports · 2026Review
- Production of bioactive cytokines using plant expression system for cardiovascular cell differentiation from human pluripotent stem cells.Stem cell research & therapy · 2025Article
- Toward the latest advancements in cardiac regeneration using induced pluripotent stem cells (iPSCs) technology: approaches and challenges.Journal of translational medicine · 2024Review
- Review
- Wnt Signaling in Atherosclerosis: Mechanisms to Therapeutic Implications.Biomedicines · 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
- Heart in a dish - choosing the right in vitro model.Disease models & mechanisms · 2023Article
- Networks that Govern Cardiomyocyte Proliferation to Facilitate Repair of the Injured Mammalian Heart.Methodist DeBakey cardiovascular journal · 2023Review
- Hypoxia is fine-tuned by Hif-1α and regulates mesendoderm differentiation through the Wnt/β-Catenin pathway.BMC biology · 2022Article
- A review of protocols for human iPSC culture, cardiac differentiation, subtype-specification, maturation, and direct reprogramming.STAR protocols · 2022Review
- Tissue Engineering Techniques for Induced Pluripotent Stem Cell Derived Three-Dimensional Cardiac Constructs.Tissue engineering. Part B, Reviews · 2022Review
- Scalable manufacturing of clinical-grade differentiated cardiomyocytes derived from human-induced pluripotent stem cells for regenerative therapy.Cell proliferation · 2022Review
- Cardiomyocytes induced from hiPSCs by well-defined compounds have therapeutic potential in heart failure by secreting PDGF-BB.Signal transduction and targeted therapy · 2022Article
- Systems for the Functional Evaluation of Human Heart Tissues Derived from Pluripotent Stem Cells.Stem cells (Dayton, Ohio) · 2022Review
- The role of metabolism in directed differentiation versus trans-differentiation of cardiomyocytes.Seminars in cell & developmental biology · 2022Review
- Review
- Article
- Epigenetic Regulation of Cardiomyocyte Differentiation from Embryonic and Induced Pluripotent Stem Cells.International journal of molecular sciences · 2021Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
rationaleHuman embryonic stem cells can form cardiomyocytes when cultured under differentiation conditions. Although the initiating step of mesoderm formation is well characterized, the subsequent steps that promote for cardiac lineages are poorly understood and limit the yield of cardiomyocytes.
objectiveOur aim was to develop a human embryonic stem cell-based high-content screening assay to discover small molecules that drive cardiogenic differentiation after mesoderm is established to improve our understanding of the biology involved. Screening of libraries of small-molecule pathway modulators was predicted to provide insight into the cellular proteins and signaling pathways that control stem cell cardiogenesis. METHODS AND
resultsApproximately 550 known pathway modulators were screened in a high-content screening assay, with hits being called out by the appearance of a red fluorescent protein driven by the promoter of the cardiac-specific MYH6 gene. One potent small molecule was identified that inhibits transduction of the canonical Wnt response within the cell, which demonstrated that Wnt inhibition alone was sufficient to generate cardiomyocytes from human embryonic stem cell-derived mesoderm cells. Transcriptional profiling of inhibitor-treated compared with vehicle-treated samples further indicated that inhibition of Wnt does not induce other mesoderm lineages. Notably, several other Wnt inhibitors were very efficient in inducing cardiogenesis, including a molecule that prevents Wnts from being secreted by the cell, which confirmed that Wnt inhibition was the relevant biological activity.
conclusionsPharmacological inhibition of Wnt signaling is sufficient to drive human mesoderm cells to form cardiomyocytes; this could yield novel tools for the benefit of pharmaceutical and clinical applications.
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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.