Project description:Loss of pancreatic Beta cell mass, identity, and function contribute to the development of diabetes. Here, we show that the endoplasmic reticulum (ER) calcium sensor, stromal interaction molecule 1 (STIM1), is critical for the maintenance of Beta cell function in female mice. When mice with Beta cell- specific deletion of STIM1 (STIM1-delta-Beta) were challenged with high-fat diet, Beta cell dysfunction was observed in female, but not male, mice. Impaired glucose tolerance was accompanied by reductions in Beta cell mass, a concomitant increase in alpha cell mass, and significant reductions in the expression of markers of Beta cell maturity, including MafA and UCN3. Mechanistic assays demonstrated that the sexually dimorphic phenotype observed in STIM1-Delta-Beta mice was due in part to loss of signaling through the noncanonical 17-Beta estradiol receptor, GPER1. Together, these data suggest that STIM1 orchestrates pancreatic Beta cell function and identity through GPER1- mediated estradiol signaling.
Project description:β-Hydroxybutyrylation (kbhb) is a new type of post-translational modification(PTM) of lysine acylation. In recent years, kbhb modification has been shown to be involved in energy metabolism, tumor metabolism, DNA damage repair and other processes. Currently, lysine β-hydroxybutyrylation has not been studied in cardiac tissue. In this study, we performed proteomic and β-hydroxybutyrylation modification omics analysis of mouse heart tissue based on LC-MS/MS analysis. These data provide the first mammalian cardiac kbhb dataset and provide new directions for further investigation of the function of kbhb in non-histone proteins.
Project description:To investigate the function of MAFB in the regulation of human beta cell identity and maturity, we established EndoCbH2 cell lines in which MAFB has been knocked down by shRNA. We then performed gene expression profiling analysis using data obtained from bulkRNA-seq of 3 biological replicates.
Project description:The investigation of the association of long non-coding RNAs (lncRNAs) with DNMT1 by RIP-seq reveals that DNMT1 interacts with DACOR1. We identified the genomic occupancy sites of DACOR1 through ChIRP-seq, which we found to significantly overlap with known differentially methylated regions (DMRs) in colon tumors. Induction of DACOR1 in colon cancer cell lines significantly reduced their ability to form colonies in vitro, suggesting a growth suppressor function. Consistent with the observed phenotype, induction of DACOR1 led to the activation of tumor-suppressor pathways and attenuation of cancer-associated metabolic pathways. Notably, DACOR1 induction resulted in down-regulation of Cystathionine β-synthase (CBS), which is known to lead to increased levels of S-adenosyl methionine (SAM) – the key methyl donor for DNA methylation.
Project description:Aims/ hypothesis: p21 (Cdc42/Rac1) activated Kinase 1 (PAK1) is depleted in type 2 diabetic human islets compared to non-diabetic (ND) human islets, and acute PAK1 restoration to type 2 diabetic human islets can restore insulin secretory function ex vivo. We hypothesized that beta cell specific PAK1 enrichment in vivo carries the capacity to mitigate high-fat diet-induced glucose intolerance by increasing the functional beta cell mass. Methods: Type 2 diabetic or ND human islets expressing exogenous PAK1 specifically in beta cells were used for bulk RNA-sequencing (RNA-seq). Human EndoC-