![]() The transcription factor c-Maf (encoded by Maf) belongs to the AP-1 family of basic region and leucine zipper transcription factors, and has been shown to be involved in the regulation of a broad array of biological processes, including lens and bone development, apoptosis, oncogenesis, and the immune response. Especially, the spatial differentiation and compartmentalization of enterocytes along the SI villus axis, including the zonated expression of many nutrient transporters, have highlighted the complexity of differentiated enterocytes and their role in nutrient sensing and absorption ( Moor et al., 2018 Harnik et al., 2021). Similarly, enterocytes also exhibit regionality in nutrient function along the intestine as well as along the crypt–villus axis ( Moor et al., 2018 Seiler et al., 2019 Gebert et al., 2020 Wang et al., 2020 Burclaff et al., 2022). ![]() This adaptation is achieved by dynamically matching the expression of specific types of brush-border enzymes and nutrient transporters to the availability of the respective dietary substrates ( Diamond and Karasov, 1987 Mochizuki et al., 2010 Sullivan et al., 2021). Collectively, our data identified c-Maf as a key regulator of SI enterocyte differentiation and function, essential for nutrient, immune, and microbial homeostasis.Īn important aspect of nutrient absorption is the ability of enterocytes to perceive and dynamically adapt to fluctuating concentrations of different dietary constituents to maximize absorptive efficiency. 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. ![]() Consequently, epithelial cell–specific c-Maf deletion resulted in impaired enterocyte maturation and nutrient uptake, including defects in the adaptation to different nutrient availability. Specifically, gene programs controlling carbohydrate and protein absorption were c-Maf–dependent. Functionally, enterocytes required c-Maf to appropriately differentiate along the villus axis. c-Maf expression was determined by opposing Noggin/BMP signals and overlapped with the zonated enrichment of nutrient transporters in the mid-villus region. Here, we identify c-Maf as an enterocyte-specific transcription factor within the SI epithelium. However, the molecular regulators governing enterocytes have remained undefined. Enterocytes are the major epithelial cell type facilitating nutrient sensing and uptake. The primary function of the small intestine (SI) is to absorb nutrients to maintain whole-body energy homeostasis.
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