FOXO1 Is Present in Stomach Epithelium and Determines Gastric Cell Distribution
Abstrak
Background and Aims Stomach cells can be converted to insulin-producing cells by Neurog3, MafA, and Pdx1 overexpression. Enteroendocrine cells can be similarly made to produce insulin by the deletion of FOXO1. Characteristics and functional properties of FOXO1-expressing stomach cells are not known. Methods Using mice bearing a FOXO1-GFP knock-in allele and primary cell cultures, we examined the identity of FOXO1-expressing stomach cells and analyzed their features through loss-of-function studies with red-to-green fluorescent reporters. Results FOXO1 localizes to a subset of Neurog3 and parietal cells. FOXO1 deletion ex vivo or in vivo using Neurog3-cre or Atp4b-cre increased numbers of parietal cells, generated insulin- and C-peptide-immunoreactive cells, and raised Neurog3 messenger RNA. Gene expression and ChIP-seq experiments identified the cell cycle regulator cyclin E1 (CCNE1) as a FOXO1 target. Conclusion FOXO1 is expressed in a subset of stomach cells. Its ablation increases parietal cells and yields insulin-immunoreactive cells, consistent with a role in lineage determination.
Topik & Kata Kunci
Penulis (7)
Wendy M. McKimpson
Taiyi Kuo
T. Kitamoto
Sei Higuchi
J. Mills
R. Haeusler
D. Accili
Akses Cepat
- Tahun Terbit
- 2022
- Bahasa
- en
- Total Sitasi
- 5×
- Sumber Database
- Semantic Scholar
- DOI
- 10.1016/j.gastha.2022.05.005
- Akses
- Open Access ✓