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Intestinal epithelial c-Maf expression determines enterocyte differentiation and nutrient uptake in mice.


ABSTRACT: The primary function of the small intestine (SI) is to absorb nutrients to maintain whole-body energy homeostasis. Enterocytes are the major epithelial cell type facilitating nutrient sensing and uptake. However, the molecular regulators governing enterocytes have remained undefined. Here, we identify c-Maf as an enterocyte-specific transcription factor within the SI epithelium. c-Maf expression was determined by opposing Noggin/BMP signals and overlapped with the zonated enrichment of nutrient transporters in the mid-villus region. Functionally, enterocytes required c-Maf to appropriately differentiate along the villus axis. Specifically, gene programs controlling carbohydrate and protein absorption were c-Maf-dependent. Consequently, epithelial cell-specific c-Maf deletion resulted in impaired enterocyte maturation and nutrient uptake, including defects in the adaptation to different nutrient availability. Concomitantly, intraepithelial lymphocytes were less abundant, while commensal epithelial cell-attaching SFB overgrew in a c-Maf-deficient environment, highlighting the close interdependence between the intestinal epithelium, immune system, and microbiota. Collectively, our data identified c-Maf as a key regulator of SI enterocyte differentiation and function, essential for nutrient, immune, and microbial homeostasis.

SUBMITTER: Cosovanu C 

PROVIDER: S-EPMC9486084 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Intestinal epithelial c-Maf expression determines enterocyte differentiation and nutrient uptake in mice.

Cosovanu Catalina C   Resch Philipp P   Jordan Stefan S   Lehmann Andrea A   Ralser Markus M   Farztdinov Vadim V   Spranger Joachim J   Mülleder Michael M   Brachs Sebastian S   Neumann Christian C  

The Journal of experimental medicine 20220919 12


The primary function of the small intestine (SI) is to absorb nutrients to maintain whole-body energy homeostasis. Enterocytes are the major epithelial cell type facilitating nutrient sensing and uptake. However, the molecular regulators governing enterocytes have remained undefined. Here, we identify c-Maf as an enterocyte-specific transcription factor within the SI epithelium. c-Maf expression was determined by opposing Noggin/BMP signals and overlapped with the zonated enrichment of nutrient  ...[more]

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