ArticleThe Journal of clinical investigation2019
Targeted demethylation at the CDKN1C/p57 locus induces human β cell replication.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 66 citations in OpenAlex.
- Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026Review
- Identification of type 2 diabetes- and obesity-associated human β-cells using deep transfer learning.eLife · 2025Article
- Abundant Parent-of-origin Effect eQTL: The Framingham Heart Study.bioRxiv : the preprint server for biology · 2025Article
- Epigenetic memory as crucial contributing factor in directing the differentiation of human iPSC into pancreatic β-cells in vitro.Cell and tissue research · 2025Review
- On correlative and causal links of replicative epimutations.Trends in genetics : TIG · 2025Review
- Harnessing beta-cell replication: advancing molecular insights to regenerative therapies in diabetes.Frontiers in endocrinology · 2025Review
- Therapeutic Strategies for Angiogenesis Based on Endothelial Cell Epigenetics.Journal of cardiovascular translational research · 2024Review
- Atypical KCNQ1/Kv7 channel function in a neonatal diabetes patient: Hypersecretion preceded the failure of pancreatic β-cells.iScience · 2024Article
- Differential CpG methylation at Nnat in the early establishment of beta cell heterogeneity.Diabetologia · 2024Article
- Epigenetics in diabetic cardiomyopathy.Clinical epigenetics · 2024Review
- Structure-Function Analysis of p57KIP2 in the Human Pancreatic Beta Cell Reveals a Bipartite Nuclear Localization Signal.Endocrinology · 2023Article
- LncRNA SNHG8 regulates the migration and angiogenesis of pHUVECs induced by high glucose via the TRPM7/ERKScientific reports · 2023Article
- Genes with epigenetic alterations in human pancreatic islets impact mitochondrial function, insulin secretion, and type 2 diabetes.Nature communications · 2023Article
- A critical review on therapeutic approaches of CRISPR-Cas9 in diabetes mellitus.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- Differential CpG methylation atbioRxiv : the preprint server for biology · 2023Article
- Identification and validation of core genes for type 2 diabetes mellitus by integrated analysis of single-cell and bulk RNA-sequencing.European journal of medical research · 2023Article
- TET (Ten-eleven translocation) family proteins: structure, biological functions and applications.Signal transduction and targeted therapy · 2023Review
- Article
- Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study.Signal transduction and targeted therapy · 2023Review
- Review
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14 authors at 2 institutions in 2 countries.
Funding
Abstract
The loss of insulin-secreting β cells is characteristic among type I and type II diabetes. Stimulating proliferation to expand sources of β cells for transplantation remains a challenge because adult β cells do not proliferate readily. The cell cycle inhibitor p57 has been shown to control cell division in human β cells. Expression of p57 is regulated by the DNA methylation status of the imprinting control region 2 (ICR2), which is commonly hypomethylated in Beckwith-Wiedemann syndrome patients who exhibit massive β cell proliferation. We hypothesized that targeted demethylation of the ICR2 using a transcription activator-like effector protein fused to the catalytic domain of TET1 (ICR2-TET1) would repress p57 expression and promote cell proliferation. We report here that overexpression of ICR2-TET1 in human fibroblasts reduces p57 expression levels and increases proliferation. Furthermore, human islets overexpressing ICR2-TET1 exhibit repression of p57 with concomitant upregulation of Ki-67 while maintaining glucose-sensing functionality. When transplanted into diabetic, immunodeficient mice, the epigenetically edited islets show increased β cell replication compared with control islets. These findings demonstrate that epigenetic editing is a promising tool for inducing β cell proliferation, which may one day alleviate the scarcity of transplantable β cells for the treatment of diabetes.
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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.