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Declining FXR expression coordinates neonatal beta cell mass development with microbial bile acid metabolism maturation in mice

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE241408 | GEO | 2025/11/06

REPOSITORIES: GEO

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Declining FXR expression coordinates neonatal beta cell mass development with microbial bile acid metabolism maturation in mice

Project description:Declining FXR expression coordinates neonatal beta cell mass development with microbial bile acid metabolism maturation in mice

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An FXR-Casp6 axis-mediated bile acid/gut microbiota sensing modulates neonatal β-cell mass expansion [scATAC-Seq]

Project description:Weaning diet switch brings gut microbiome maturation along with postnatal formation of sufficient matured β-cell mass. The matured gut microbiota elevated agonistic components of bile acid (BA) pool towards farnesoid X receptor (FXR) that was paralleling with the declined β-cell FXR expression. To investigate whether BA/FXR could link postnatal β-cell development and gut microbiota maturation, we forced persistent FXR expression in β cells (βFxrKI) and found decreased neonatal β-cell mass growth and increased glycemia in weaned βFxrKI mice, which could be partially recovered by ablating gut microbiota before weaning. scRNA and scATAC seq analysis showed different β cell growth trajectories with suppressed intrinsic cell proliferation and elevated cell apoptosis in βFxrKI. Caspase-6 was then identified as a dominant β-cell FXR downstream effector to mediate its regulation. The negative regulation of the FXR-Casp6 axis on postnatal β-cell mass expansion reflected a programmed cellular response to gut microbiota maturation in neonatal mice.

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