GPRC5B preserves a mature β-cell state in obesity by controlling MafA expression [dof92_RNA-seq]
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ABSTRACT:
PROVIDER: PRJNA1306579 | ENA |
REPOSITORIES: ENA
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Project description:In vitro studies have implicated orphan receptor GPRC5B in β-cell survival, proliferation and insulin secretion, but its relevance for glucose homeostasis in vivo is largely unknown. Using tamoxifen-inducible, β-cell-specific GPRC5B knockout mice (Ins-G5b-KOs) we show here that loss of GPRC5B does not affect β-cell function in the lean state, but results in strongly reduced insulin secretion and disturbed glucose tolerance in mice subjected to high fat diet for 16 weeks. Flow cytometry and single-cell expression analyses in islets from obese mice show a reduced β-cell abundance and a less mature β-cell phenotype in Ins-G5b-KOs. Expression of β-cell-specific transcription factor MafA is reduced both on the RNA and protein level, as are transcripts of MafA target genes. Mechanistically, we show that phosphorylation of cAMP response element-binding protein (CREB), a major regulator of MafA expression, is reduced in islets of obese Ins-G5b-KOs, and that this phenotype precedes the downregulation of MafA and MafA target genes. Taken together, GPRC5B helps to maintain mature β-cell function in obesity through cAMP/CREB-dependent regulation of MafA expression.
2025-08-26 | GSE305580 | GEO
Project description:In vitro studies have implicated orphan receptor GPRC5B in β-cell survival, proliferation and insulin secretion, but its relevance for glucose homeostasis in vivo is largely unknown. Using tamoxifen-inducible, β-cell-specific GPRC5B knockout mice (Ins-G5b-KOs) we show here that loss of GPRC5B does not affect β-cell function in the lean state, but results in strongly reduced insulin secretion and disturbed glucose tolerance in mice subjected to high fat diet for 16 weeks. Flow cytometry and single-cell expression analyses in islets from obese mice show a reduced β-cell abundance and a less mature β-cell phenotype in Ins-G5b-KOs. Expression of β-cell-specific transcription factor MafA is reduced both on the RNA and protein level, as are transcripts of MafA target genes. Mechanistically, we show that phosphorylation of cAMP response element-binding protein (CREB), a major regulator of MafA expression, is reduced in islets of obese Ins-G5b-KOs, and that this phenotype precedes the downregulation of MafA and MafA target genes. Taken together, GPRC5B helps to maintain mature β-cell function in obesity through cAMP/CREB-dependent regulation of MafA expression.
2025-08-26 | GSE305588 | GEO
Project description:GPRC5B preserves a mature β-cell state in obesity by controlling MafA expression
| PRJNA1306586 | ENA
Project description:GPRC5B preserves a mature β-cell state in obesity by controlling MafA expression [dof105_scRNA-seq]
| PRJNA1306588 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-08-26 | GSE305589 | GEO
Project description:To investigate whether loss of GPRC5B affects macrophage function, we generated myeloid-specific Gprc5b knockout mice and then did RNA-seq using resident peritoneal macrophage to analyze the gene expression profile.
2025-01-02 | GSE261584 | GEO
Project description:To investigate whether loss of GPRC5B affects macrophage function, we generated myeloid-specific Gprc5b knockout mice and then did RNA-seq using bone marrow-derived M0 macrophages to analyze the gene expression profile.
2025-01-02 | GSE261586 | GEO
Project description:MafA and MafB transcription factors have been shown to be key regulators of insulin and glucagon transcription. MafB is essential for alpha and beta cell differentiation, as MafB deficient mice produced fewer insulin+ and glucagon+ cells during development, with MafA expressed in remaining insulin+ cells. In contrast, beta cell development was reported to be normal in a total MafA knock out, although the animals developed beta cell dysfunction and diabetes as adults. However, we have found that MafB expression is elevated during development and retained in adult insulin+ cells after conditional removal of MafA in the pancreas. These studies will evaluate the broader significance of these insulin and glucagon regulators in alpha and beta cell development and function. Our efforts will focus on determining if the concerted actions of MafA and MafB factors are significant to beta cell formation, and we specifically plan to: Determine how alpha and beta cell differentiation is affected in MafA/MafB compound mutant mice during pancreas development. cDNA microarray studies (pancchip 6.0) with wild type, MafAKO, MafB-/-, and MafAKOMafB-/- mutant E18.5 pancreata will be performed to comprehensively identify genes controlled by MafA and MafB in developing alpha and beta cells.
2014-11-04 | E-MTAB-3070 | biostudies-arrayexpress
Project description:Gprc5b, a retinoic acid-inducible orphan G protein–coupled receptor, is a member of the group C metabotropic glutamate receptor family. Its function is unknown. However, recent evidence suggests that it binds Frizzled Wnt receptors and may activate noncanonical Wnt signaling pathways. Here we report the discovery of a brain-enriched C-terminal splice variant of Gprc5b, Gprc5b_v2, by cDNA microarray and RT-PCR analyses. The variant appeared to have been downregulated in the brains of learning/memory-deficient p97FE65 null mice. Despite the fact that the mice had been backcrossed with the C57Bl/6J strain for more than ten generations, Gprc5b and other genes surrounding the FE65 locus on mouse chromosome 7 were retained from the 129-derived ES cells used to generate the knockout line. The differential splicing is unlikely due to FE65 function, as originally suspected, as Gprc5b_v2 expression is also downregulated in the brains of 129/Sv substrains in comparison to C57Bl/6J mice. Further characterization revealed the expression of both Gprc5b_v2 and the previously described variant, Gprc5b_v1, in neurons. Interestingly, Gprc5b_v2 mRNA levels increase with neuronal maturation, paralleling the expression of synaptic proteins involved in the regulation of synaptic plasticity. Finally, we report evidence that both Gprc5b_v2 and Gprc5b_v1 regulate neurite outgrowth. These results are consistent with a putative function of Gprc5b in noncanonical Wnt signaling, which play roles in the regulation of neuronal morphology, and the formation and modulation of neuronal circuitry. Cerebral cortex tissues were dissected from five FE65 wild-type and p97FE65 null littermate pairs (6 months of age)
2010-12-12 | E-GEOD-14274 | biostudies-arrayexpress