ArticleScientific reports2019
Deciphering Role of Wnt Signalling in Cardiac Mesoderm and Cardiomyocyte Differentiation from Human iPSCs: Four-dimensional control of Wnt pathway for hiPSC-CMs differentiation.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 98 citations in OpenAlex.
- Developmentally Inspired Bioprinting of Nascent Multicellular Human Heart Tissue Through In Situ Differentiation and Morphogenesis of iPSCs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Sustained β-catenin activation via GSK3 inhibition promotes direct fibroblast-to-cardiomyocyte reprogramming.The Journal of biological chemistry · 2026Article
- Electrical coupling between transplanted cardiomyocytes and host myocardium to prevent arrhythmia.Disease models & mechanisms · 2026Review
- Actomyosin contractility is a potent suppressor of mesoderm induction by human pluripotent stem cells.The Journal of cell biology · 2026Article
- 3D Bioprinted Fat-Myocardium Model Unravels the Role of Adipocyte Hypertrophy in Atrial Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Early multi-omic signatures and machine learning models predict cardiomyocyte differentiation efficiency and enable robust hPSC differentiation to cardiomyocytes.bioRxiv : the preprint server for biology · 2026Article
- Engineered heart tissues formed with cardiac progenitors and differentiated cardiomyocytes exhibit similar physiologic properties at differentiation-matched timepoints.Biofabrication · 2025Article
- MitoScribe single-cell molecular recorder logs graded signaling dynamics into mitochondrial DNA.bioRxiv : the preprint server for biology · 2025Article
- Geometrically Controlled WNT Activation Drives Intestinal Morphogenesis.Advanced healthcare materials · 2025Article
- Novel miRNAs, miR-937-3p, miR-4536-3p, and miR-4650-5p, can Modulate Neuronal Differentiation via the Wnt/MAPK Pathway in SH-SY5Y Cells.Molecular neurobiology · 2025Article
- Synthetic thermoresponsive scaffolds for the expansion and differentiation of human pluripotent stem cells into cardiomyocytes.RSC advances · 2025Article
- Engineering a controlled cardiac multilineage co-differentiation process using statistical design of experiments.Stem cell research & therapy · 2025Article
- Seamless integration of CMOS microsensors into open microfluidic systems.Lab on a chip · 2025Article
- AnMaterials today. Bio · 2025Article
- Cathepsin K inhibition promotes efficient differentiation of human embryonic stem cells to mature cardiomyocytes by mediating glucolipid metabolism and cellular energy homeostasis.Stem cell research & therapy · 2025Article
- Selective activation of FZD2 and FZD7 reveals non-redundant function during mesoderm differentiation.Stem cell reports · 2025Article
- HIF‑1α overexpression improves the efficacy of human induced pluripotent stem cell‑derived cardiomyocytes for cardiac repair following myocardial infarction.Molecular medicine reports · 2025Article
- Targeting Canonical Wnt-signaling Through GSK-3β in Arrhythmogenic Cardiomyopathy: Conservative or Progressive?Journal of cardiovascular translational research · 2025Review
- c-JUN: a chromatin repressor that limits mesoderm differentiation in human pluripotent stem cells.Nucleic acids research · 2025Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Differentiation of cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) is critically dependent upon the regulation of the Wnt signaling pathway. The mechanisms remain unclear with regard to the dose and timing of each differentiation inducer, and the interaction of the inducers that regulate the Wnt in mesendoderm specification to cardiac mesoderm. Consequently, it remains far from optimal in differentiation efficiency and consistency from hiPSC lines to CMs. Here, we have carefully deciphered the role of Wnt signaling pathway manipulation on mesoderm specification in a dosage and time dependent manner. To examine the hypothesis of that fate specification of hiPSC-CMs differentiation is dictated by temporal and spatial factors that regulate Wnt, we evaluate hiPSC-CM differentiation with: (1) two-phase modulation of Wnt, (2) dosage variant of GSK3β inhibitors, (3) treatment with insulin, and (4) 3-dimentional suspension culture environment on iPSC-CM differentiation. The results highlight the importance of mesendoderm specification to cardiac mesoderm, which needs precisely regulation of Wnt in a dosage dependent and temporal on/off manner. This temporal regulation dictates the final efficiency and purity of derived cardiomyocytes. After the initial activation of Wnt signaling pathway to generate mesendoderm, the maintenance of Wnt signaling at an appropriate dose is critical to direct the cell fate into cardiac mesoderm. Otherwise, lower Wnt signals lead to definitive endoderm and higher Wnt signals induce presomitic mesoderm differentiation. The precisely specification of cardiac mesoderm results in not only greater than 90% of cTnT
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