國家衛生研究院 NHRI:Item 3990099045/14796
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    題名: ARID1A loss in pancreas leads to islet developmental defect and metabolic disturbance
    作者: Kuo, TL;Cheng, KH;Chen, LT;Hung, WC
    貢獻者: National Institute of Cancer Research
    摘要: ARID1A is a tumor suppressor gene mutated in 7–10% of pancreatic cancer patients. However, its function in pancreas development and endocrine regulation is unclear. We generated mice that lack Arid1a expression in the pancreas. Our results showed that deletion of the Arid1a gene in mice caused a reduction in islet numbers and insulin production, both of which are associated with diabetes mellitus (DM) phenotype. RNA sequencing of isolated islets confirmed DM gene signature and decrease of developmental lineage genes. We identified neurogenin3, a transcription factor that controls endocrine fate specification, is a direct target of Aird1a. Gene set enrichment analysis indicated the enhancement of histone deacetylase (HDAC) pathway after Arid1a depletion and a clinically approved HDAC inhibitor showed therapeutic benefit by suppressing disease onset. Our data suggest that Arid1a is required for the development of pancreatic islets by regulating Ngn3+-mediated transcriptional program and is important in maintaining endocrine function.
    日期: 2023-01-20
    關聯: iScience. 2023 Jan 20;26(1):Article number 105881.
    Link to: http://dx.doi.org/10.1016/j.isci.2022.105881
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2589-0042&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000996425500001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85145985597
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