c-MAF coordinates enterocyte zonation and nutrient uptake transcriptional programs.
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
05 12 2022
05 12 2022
Historique:
received:
03
12
2021
revised:
15
07
2022
accepted:
24
08
2022
entrez:
19
9
2022
pubmed:
20
9
2022
medline:
23
9
2022
Statut:
ppublish
Résumé
Small intestinal villi are structural and functional units present in higher vertebrates and uniquely adapted to nutrient absorption. Villus enterocytes are organized in transcriptional "zones" dedicated to specialized tasks such as absorption of specific nutrients. We report that the transcription factor c-MAF is expressed in differentiated lower and mid-villus enterocytes and is a target of BMP signaling. Maf inactivation perturbed the villus zonation program by increasing carbohydrate-related transcripts while suppressing transcripts linked to amino-acid and lipid absorption. The formation of cytoplasmic lipid droplets, shuttling dietary fat to chylomicrons, was impaired upon Maf loss indicating its role in dietary lipid handling. Maf inactivation under homeostatic conditions expanded tuft cells and led to compensatory gut lengthening, preventing weight loss. However, delayed Maf-/- enterocyte maturation impaired weight recovery after acute intestinal injury, resulting in reduced survival. Our results identify c-MAF as a regulator of the intestinal villus zonation program, while highlighting the importance of coordination between stem/progenitor and differentiation programs for intestinal regeneration.
Identifiants
pubmed: 36121415
pii: 213478
doi: 10.1084/jem.20212418
pmc: PMC9486085
pii:
doi:
Substances chimiques
Carbohydrates
0
Chylomicrons
0
Dietary Fats
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Swiss National Science Foundation
ID : CRSII5_177191
Pays : Switzerland
Organisme : University of Lausanne
Informations de copyright
© 2022 Gonzalez Loyola et al.
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