ArticleJCI insight2021
Reduced replication fork speed promotes pancreatic endocrine differentiation and controls graft size.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The trial behind it
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Modeling immune responses to autologous and allogeneic human stem cell-derived islet grafts in vivo.JCI insight · 2026Article
- A universal platform for simultaneous TCRα/β removal enables safer and more potent TCR therapies and autoimmune modeling.bioRxiv : the preprint server for biology · 2026Article
- Limitations in PPARα-dependent mitochondrial programming restrain the differentiation of human stem cell-derived β cells.Nature communications · 2025Article
- Metabolic functions for molecular chaperones and stress proteins in microcephaly.Cellular and molecular life sciences : CMLS · 2025Review
- Scale up manufacturing approach for production of human induced pluripotent stem cell-derived islets using Vertical Wheel® bioreactors.NPJ Regenerative medicine · 2025Article
- Navigating challenges in human pluripotent stem cell-derived islet therapy for type 1 diabetes.Frontiers in immunology · 2025Review
- Extracellular matrix proteins refine microenvironments for pancreatic organogenesis from induced pluripotent stem cell differentiation.Theranostics · 2025Article
- Investigating the pathogenicity of the recessivemedRxiv : the preprint server for health sciences · 2024Article
- Review
- Tankyrase inhibition promotes endocrine commitment of hPSC-derived pancreatic progenitors.Nature communications · 2024Article
- Non-invasive quantification of stem cell-derived islet graft size and composition.Diabetologia · 2024Article
- Nucleotide depletion promotes cell fate transitions by inducing DNA replication stress.Developmental cell · 2024Article
- Optimized Protocol for Generating Functional Pancreatic Insulin-secreting Cells from Human Pluripotent Stem Cells.Journal of visualized experiments : JoVE · 2024Article
- AT7867 promotes pancreatic progenitor differentiation of human iPSCs.Stem cell reports · 2023Article
- Replication stress in mammalian embryo development, differentiation, and reprogramming.Trends in cell biology · 2023Review
- Immune cell identifier and classifier (ImmunIC) for single cell transcriptomic readouts.Scientific reports · 2023Article
- Enrichment of stem cell-derived pancreatic beta-like cells and controlled graft size through pharmacological removal of proliferating cells.Stem cell reports · 2023Article
- Article
- Mitochondrial regulation in human pluripotent stem cells during reprogramming and β cell differentiation.Frontiers in endocrinology · 2023Review
- Review
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 2 countries.
Funding
Abstract
Limitations in cell proliferation are important for normal function of differentiated tissues and essential for the safety of cell replacement products made from pluripotent stem cells, which have unlimited proliferative potential. To evaluate whether these limitations can be established pharmacologically, we exposed pancreatic progenitors differentiating from human pluripotent stem cells to small molecules that interfere with cell cycle progression either by inducing G1 arrest or by impairing S phase entry or S phase completion and determined growth potential, differentiation, and function of insulin-producing endocrine cells. We found that the combination of G1 arrest with a compromised ability to complete DNA replication promoted the differentiation of pancreatic progenitor cells toward insulin-producing cells and could substitute for endocrine differentiation factors. Reduced replication fork speed during differentiation improved the stability of insulin expression, and the resulting cells protected mice from diabetes without the formation of cystic growths. The proliferative potential of grafts was proportional to the reduction of replication fork speed during pancreatic differentiation. Therefore, a compromised ability to enter and complete S phase is a functionally important property of pancreatic endocrine differentiation, can be achieved by reducing replication fork speed, and is an important determinant of cell-intrinsic limitations of growth.
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What OpenQuestion holds
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.