ArticleStem cell research & therapy2023
Photo-click hydrogels for 3D in situ differentiation of pancreatic progenitors from induced pluripotent stem cells.
Article in Stem cell research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 8 citations in OpenAlex.
- Aqueous Synthesis of Poly(ethylene glycol)-amide-Norbornene-Carboxylate for Modular Hydrogel Crosslinking.Advanced materials interfaces · 2025Article
- Generation of vascularized pancreatic progenitors through co-differentiation of endoderm and mesoderm from human pluripotent stem cells.Stem cell research & therapy · 2024Article
- Soft Polyethylene Glycol Hydrogels Support Human PSC Pluripotency and Morphogenesis.ACS biomaterials science & engineering · 2024Article
- Fast-relaxing hydrogels with reversibly tunable mechanics for dynamic cancer cell culture.Biomaterials advances · 2024Article
- Orthogonally Crosslinked Gelatin-Norbornene Hydrogels for Biomedical Applications.Macromolecular bioscience · 2024Review
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4 authors at 3 institutions in 1 country.
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Abstract
backgroundInduced pluripotent stem cells (iPSC) can be differentiated to cells in all three germ layers, as well as cells in the extraembryonic tissues. Efforts in iPSC differentiation into pancreatic progenitors in vitro have largely been focused on optimizing soluble growth cues in conventional two-dimensional (2D) culture, whereas the impact of three-dimensional (3D) matrix properties on the morphogenesis of iPSC remains elusive.
methodsIn this work, we employ gelatin-based thiol-norbornene photo-click hydrogels for in situ 3D differentiation of human iPSCs into pancreatic progenitors (PP). Molecular analysis and single-cell RNA-sequencing were utilized to elucidate on the distinct identities of subpopulations within the 2D and 3D differentiated cells.
resultsWe found that, while established soluble cues led to predominately PP cells in 2D culture, differentiation of iPSCs using the same soluble factors led to prominent branching morphogenesis, ductal network formation, and generation of diverse endoderm populations. Through single-cell RNA-sequencing, we found that 3D differentiation resulted in enrichments of pan-endodermal cells and ductal cells. We further noted the emergence of a group of extraembryonic cells in 3D, which was absent in 2D differentiation. The unexpected emergence of extraembryonic cells in 3D was found to be associated with enrichment of Wnt and BMP signaling pathways, which may have contributed to the emergence of diverse cell populations. The expressions of PP signature genes PDX1 and NKX6.1 were restored through inhibition of Wnt signaling at the beginning of the posterior foregut stage.
conclusionsTo our knowledge, this work established the first 3D hydrogel system for in situ differentiation of human iPSCs into PPs.
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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.