ArticleNature communications2023
Epithelial disruption drives mesendoderm differentiation in human pluripotent stem cells by enabling TGF-β protein sensing.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- The notochord: development, disease and stem cell-based modelling.Development (Cambridge, England) · 2026Review
- Optogenetic WNT signaling drives germ layer self-organization in a human gastruloid model.bioRxiv : the preprint server for biology · 2026Article
- MFGE-8, a Corona Protein on Extracellular Vesicles, Mediates Self-Renewal and Survival of Human Pluripotent Stem Cells.Journal of extracellular vesicles · 2025Article
- Research progress of stem cells in the treatment of atherosclerosis.Frontiers in cell and developmental biology · 2025Review
- In vitro modelling of anterior primitive streak patterning with human pluripotent stem cells identifies the path to notochord progenitors.Development (Cambridge, England) · 2024Article
- Article
- Effect of Clemizole on Alpha-Synuclein-Preformed Fibrils-Induced Parkinson's Disease Pathology: A Pharmacological Investigation.Neuromolecular medicine · 2024Article
- Dichotomous Effects of Glypican-4 on Cancer Progression and Its Crosstalk with Oncogenes.International journal of molecular sciences · 2024Article
- Glypican-4 serum levels are associated with cognitive dysfunction and vascular risk factors in Parkinson's disease.Scientific reports · 2024Article
- Article
- Differentially Expressed Genes Induced by Erythropoietin Receptor Overexpression in Rat Mammary Adenocarcinoma RAMA 37-28 Cells.International journal of molecular sciences · 2023Article
- Stabilization of cell-cell adhesions prevents symmetry breaking and locks in pluripotency in 3D gastruloids.Stem cell reports · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The processes of primitive streak formation and fate specification in the mammalian epiblast rely on complex interactions between morphogens and tissue organization. Little is known about how these instructive cues functionally interact to regulate gastrulation. We interrogated the interplay between tissue organization and morphogens by using human induced pluripotent stem cells (hiPSCs) downregulated for the morphogen regulator GLYPICAN-4, in which defects in tight junctions result in areas of disrupted epithelial integrity. Remarkably, this phenotype does not affect hiPSC stemness, but impacts on cell fate acquisition. Strikingly, cells within disrupted areas become competent to perceive the gastrulation signals BMP4 and ACTIVIN A, an in vitro surrogate for NODAL, and thus differentiate into mesendoderm. Yet, disruption of epithelial integrity sustains activation of BMP4 and ACTIVIN A downstream effectors and correlates with enhanced hiPSC endoderm/mesoderm differentiation. Altogether, our results disclose epithelial integrity as a key determinant of TGF-β activity and highlight an additional mechanism guiding morphogen sensing and spatial cell fate change within an epithelium.
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