| First Author | Cosovanu C | Year | 2022 |
| Journal | J Exp Med | Volume | 219 |
| Issue | 12 | PubMed ID | 36121416 |
| Mgi Jnum | J:357332 | Mgi Id | MGI:7448351 |
| Doi | 10.1084/jem.20220233 | Citation | Cosovanu C, et al. (2022) Intestinal epithelial c-Maf expression determines enterocyte differentiation and nutrient uptake in mice. J Exp Med 219(12) |
| abstractText | 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. |
