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The mechanisms underlying the development of complications in type 1 diabetes (T1D) are poorly understood. Disease modeling of induced pluripotent stem cells (iPSCs) from patients with longstanding T1D (disease duration ≥ 50 years) with severe (Medalist +C) or absent to mild complications (Medalist -C) revealed impaired growth, reprogramming, and differentiation in Medalist +C. Genomics and proteomics analyses suggested differential regulation of DNA damage checkpoint proteins favoring protection from cellular apoptosis in Medalist -C. In silico analyses showed altered expression patterns of DNA damage checkpoint factors among the Medalist groups to be targets of miR200, whose expression was significantly elevated in Medalist +C serum. Notably, neurons differentiated from Medalist +C iPSCs exhibited enhanced susceptibility to genotoxic stress that worsened upon miR200 overexpression. Furthermore, knockdown of miR200 in Medalist +C fibroblasts and iPSCs rescued checkpoint protein expression and reduced DNA damage. We propose miR200-regulated DNA damage checkpoint pathway as a potential therapeutic target for treating complications of diabetes.
Pubmed ID: 26244933 RIS Download
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Core that offers support for data-driven projects related to basic, clinical and translational research, with a particular emphasis on diabetes. The core aims to ensure that researchers take advantage of the most modern and robust methods available in the field of Bioinformatics and Biostatistics.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on October 27,2023. Core that provides cell sorting and flow cytometry services. Specific services include cell analysis, large object sorting,magnetic cell enrichment, and automatic cell counting.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on October 27,2023. Core that provides services for performing specific morphological procedures, providing training and access to equipment, maintaining the specialized microscopes, and giving advice and interpretation.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on October 27,2023. Core that provides technically advanced physiological evaluation of metabolism in diabetes, obesity, and their associated complications in rodents for DRC investigators and outside users. It also provides training of investigators and trainees in several physiological procedures.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on October 27,2023. Core that provides services for genetic and genomic analysis, including DNA extraction from blood, access to DNA collections from the Core?s repository, SNP genotyping, and support for gene expression studies based on both high-density oligonucleotide arrays and real-time quantitative PCR.
View all literature mentionsCore that maintains a centralized facility for the generation and propagation of reprogrammed iPS cells for use in molecular and cellular pathologies underlying diabetes and its complications.
View all literature mentionsSix component core which facilitates the exchange of research information and discussions among investigators, fellows and students within the Joslin Diabetes Center, as well as between Joslin Staff and outside researchers with similar interests.
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