ArticleNature communications2025
Improving cellular fitness of human stem cell-derived islets under hypoxia.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed.
- Review
- Engineering the oxygen microenvironment for pancreatic islet transplants.NPJ Regenerative medicine · 2026Review
- Clinical translational research on stem cell products: prospects and challenges.Signal transduction and targeted therapy · 2026Review
- Divergent cell-type specific hypoxia responses in human stem cell-derived and primary islets.Scientific reports · 2026Article
- Enhanced hypoxia resistance distinguishes human pluripotent stem cell-derived islets from primary islets.American journal of physiology. Cell physiology · 2026Article
- A loss of function variant inmedRxiv : the preprint server for health sciences · 2026Article
- Neoepitopes at the crossroads of immunometabolism: metabolic remodeling of antigen presentation in type 1 diabetes.Frontiers in immunology · 2026Review
- Article
- Stable intracranial imaging of dura mater-engrafted pancreatic islet cells in awake mice.Nature communications · 2025Article
- Assessment of protein synthesis rate enables metabolic profiling of resident-immune cells of the islets of Langerhans.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Stem cell-derived islet cell therapy can effectively treat type 1 diabetes, but its efficacy is hindered by low oxygen supply post-transplantation, particularly in subcutaneous spaces and encapsulation devices, leading to cell dysfunction. The response to hypoxia and effective strategies to alleviate its detrimental effects remain poorly understood. Here, we show that β cells within stem cell-derived islets gradually undergo a decline in cell identity and metabolic function in hypoxia. This is linked to reduced expression of immediate early genes (EGR1, FOS, and JUN), which downregulates key β cell transcription factors. We further identified genes important for maintaining β cell fitness in hypoxia, with EDN3 as a potent player. Elevated EDN3 expression preserves β cell identity and function in hypoxia by modulating genes involved in β cell maturation, glucose sensing and regulation. These insights improve the understanding of hypoxia's impact on stem cell-derived islets, offering a potential intervention for 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.