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Id3 upregulates BrdU incorporation associated with a DNA damage response, not replication, in human pancreatic β-cells.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Cell cycle visualization tools to study cardiomyocyte proliferation in real-time.Open biology · 2024Review
- DNA hypomethylation activates Cdk4/6 and Atr to induce DNA replication and cell cycle arrest to constrain liver outgrowth in zebrafish.Nucleic acids research · 2024Article
- Approaches to Inducing β-Cell Regeneration.Biomedicines · 2022Review
- XBP1u Is Involved in C2C12 Myoblast DifferentiationFrontiers in physiology · 2022Article
- ID3 promotes homologous recombination via non-transcriptional and transcriptional mechanisms and its loss confers sensitivity to PARP inhibition.Nucleic acids research · 2021Article
- Article
- In vivo pulse labeling of isochronic cohorts of cells in the central nervous system using FlashTag.Nature protocols · 2018Article
- ID3 regulates the MDC1-mediated DNA damage response in order to maintain genome stability.Nature communications · 2017Article
- Contribution of Inhibitor of DNA Binding/Differentiation-3 and Endocrine Disrupting Chemicals to Pathophysiological Aspects of Chronic Disease.BioMed research international · 2017Review
- A Pdx-1-Regulated Soluble Factor Activates Rat and Human Islet Cell Proliferation.Molecular and cellular biology · 2016Article
- Activation of GPR119 Stimulates Human β-Cell Replication and Neogenesis in Humanized Mice with Functional Human Islets.Journal of diabetes research · 2016Article
- Article
- Repurposing cAMP-modulating medications to promote β-cell replication.Molecular endocrinology (Baltimore, Md.) · 2014Article
- Escherichia coli-derived outer membrane vesicles are genotoxic to human enterocyte-like cells.Infectious agents and cancer · 2014Article
- Migration path of stem cells involved in the repair of damaged pancreatic tissue caused by pancreatitis.International journal of clinical and experimental pathology · 2014Article
- Quality of Air-Transported Human Islets for Single Islet Cell Preparations.Cell medicine · 2013Article
- Ku70 functions in addition to nonhomologous end joining in pancreatic β-cells: a connection to β-catenin regulation.Diabetes · 2013Article
- Stimulating β-cell regeneration by combining a GPR119 agonist with a DPP-IV inhibitor.PloS one · 2013Article
- Article
- Overexpression of hepatocyte nuclear factor-4α initiates cell cycle entry, but is not sufficient to promote β-cell expansion in human islets.Molecular endocrinology (Baltimore, Md.) · 2012Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Elucidating mechanisms of cell cycle control in normally quiescent human pancreatic β-cells has the potential to impact regeneration strategies for diabetes. Previously we demonstrated that Id3, a repressor of basic Helix-Loop-Helix (bHLH) proteins, was sufficient to induce cell cycle entry in pancreatic duct cells, which are closely related to β-cells developmentally. We hypothesized that Id3 might similarly induce cell cycle entry in primary human β-cells. To test this directly, adult human β-cells were transduced with adenovirus expressing Id3. Consistent with a replicative response, β-cells exhibited BrdU incorporation. Further, Id3 potently repressed expression of the cyclin dependent kinase inhibitor p57 (Kip2 ) , a gene which is also silenced in a rare β-cell hyperproliferative disorder in infants. Surprisingly however, BrdU positive β-cells did not express the proliferation markers Ki67 and pHH3. Instead, BrdU uptake reflected a DNA damage response, as manifested by hydroxyurea incorporation, γH2AX expression, and 53BP1 subcellular relocalization. The uncoupling of BrdU uptake from replication raises a cautionary note about interpreting studies relying solely upon BrdU incorporation as evidence of β-cell proliferation. The data also establish that loss of p57 (Kip2) is not sufficient to induce cell cycle entry in adult β-cells. Moreover, the differential responses to Id3 between duct and β-cells reveal that β-cells possess intrinsic resistance to cell cycle entry not common to all quiescent epithelial cells in the adult human pancreas. The data provide a much needed comparative model for investigating the molecular basis for this resistance in order to develop a strategy for improving replication competence in β-cells.
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