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TET-dependent signaling of β-cell underlies intrauterine hyperglycemia-induced glucose intolerance in offspring [scRNA-seq]

ABSTRACT: Epidemiologically, gestational diabetes mellitus (GDM) increases offspring’s diabetes risk. Intrauterine hyperglycemia (IHG) is a typical characteristic of GDM, impairing offspring’s glucose tolerance and insulin secretion, but the underlying mechanisms remain unclear. Here, we found IHG downregulates DNA demethylases Tet2/3 in fetal pancreatic islets. Pancreas-specific Tet2/3 double knockout (DKO) recapitulates the IHG effects. scRNA-seq analysis shows IHG or DKO downregulates β-cell signature while upregulating δ-cell signature.

ORGANISM(S): Mus musculus

PROVIDER: GSE288095 | GEO | 2025/12/31

REPOSITORIES: GEO

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Project description:Genomic expression profiles of blood and placenta reveal significant immune-related pathways and categories in Chinese women with Gestational Diabetes Gestational diabetes mellitus (GDM) is a complex metabolic disease which occurs in pregnancy with high prevalence, and its pathogenesis remains elusive. Thus far, there has been no comprehensive gene expression profiling in Chinese women with GDM. In this study, we attempt to define the genes and/or pathways that are involved in GDM with Chinese ethnicity, by the Illumina microarray technique. We found 5,197 and 243 genes with significantly altered expression due to GDM in blood and placenta tissues, respectively. Previously known genes (such as TNF, IL1B, LEP, IFNG, and HLA-G) with altered gene expression in GDM were also validated here. In addition, we identified undescribed genes VAV3, PTPN6, CD48 and IL15, in which expression was related to GDM by microarray and Q-RT-PCR assays. To identify GDM-associated pathways, we used analyses with integrated functional annotation (i.e. KEGG) and extracted two significant pathways, which were Natural killer cell mediated cytotoxicity (hsa04650; FDR = 7.10E-09) in blood and Cytokine-cytokine receptor interaction (hsa04060; FDR = 1.07E-03) in placenta tissues. Immune system process (GO: 0002376) was identified by GO analysis with FDR P-value = 7.01E-60 in blood and FDR P-value = 3.57E-08 in placenta tissues, indicating the importance of immunological and inflammatory categories in GDM. Furthermore, despite differences in the quantity of gene expression, we observed a similar functional distribution between expression of blood and placenta tissues in GDM under the categories of immunity. These newly identified key genes and pathways may provide valuable information for the pathogenesis of GDM and advance disease diagnosis, prevention, medication design, and clinical treatment of the disease. One individual GDM blood tissue sample and one pooled GDM blood tissue sample were compared to one pooled healthy blood tissue sample. One pooled GDM placenta tissue sample was compared to one pooled healthy placenta tissue sample.

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TET-dependent signaling of β-cell underlies intrauterine hyperglycemia-induced glucose intolerance in offspring [scRNA-seq]

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