FOXO1 Is Present in Stomach Epithelium and Determines Gastric Cell Distribution.

Autor:	McKimpson WM; Division of Endocrinology, Department of Medicine, Columbia University, New York, New York.; Naomi Berrie Diabetes Center, Columbia University, New York, New York., Kuo T; Division of Endocrinology, Department of Medicine, Columbia University, New York, New York.; Naomi Berrie Diabetes Center, Columbia University, New York, New York., Kitamoto T; Division of Endocrinology, Department of Medicine, Columbia University, New York, New York.; Naomi Berrie Diabetes Center, Columbia University, New York, New York., Higuchi S; Naomi Berrie Diabetes Center, Columbia University, New York, New York.; Department of Pathology and Cell Biology, Columbia University, New York, New York., Mills JC; Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas., Haeusler RA; Naomi Berrie Diabetes Center, Columbia University, New York, New York.; Department of Pathology and Cell Biology, Columbia University, New York, New York., Accili D; Division of Endocrinology, Department of Medicine, Columbia University, New York, New York.; Naomi Berrie Diabetes Center, Columbia University, New York, New York.
Jazyk:	angličtina
Zdroj:	Gastro hep advances [Gastro Hep Adv] 2022; Vol. 1 (5), pp. 733-745. Date of Electronic Publication: 2022 May 14.
DOI:	10.1016/j.gastha.2022.05.005
Abstrakt:	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. Competing Interests: Conflicts of Interest: These authors disclose the following: D.A. was a founder, director, stock holder, and chair of board of Forkhead Biotherapeutics Corp. The remaining authors disclose no conflicts.
Databáze:	MEDLINE
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