Year: 2022
Type: article
Abstract: BACKGROUND AND AIMS: Stomach cells can be converted to insulin-producing cells by Neurog3, MafA, and Pdxl over-expression. 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.
Source: Gastro Hep Advances
Institutions: Columbia University, Baylor College of Medicine
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,000
Awards: Role of Forkhead proteins in insulin action, Gut cell plasticity during diabetes treatment, G2299247446, Mechanisms linking insulin action with lipoprotein metabolism, Becton Dickinson LSR II Analytical Flow Cytometer, G706334092, Epigenetic Regulation by FoxO1 in Pancreatic Beta Cells, Clinical and Translational Science Award, REGULATION OF ATROPHY-INDUCED PROGENITOR CELLS IN THE GASTRIC CORPUS, Columbia Diabetes Research Center, Texas Medical Center Digestive Diseases Center, Mechanisms of Beta Cell Failure, Postdoctoral Training in Arteriosclerosis Research
OpenAlex ID: W4280633855