FOXO1 Is Present in Stomach Epithelium and Determines Gastric Cell Distribution
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Gastro Hep Advances |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772572322000838 |
| _version_ | 1811210294965305344 |
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| author | Wendy M. McKimpson Taiyi Kuo Takumi Kitamoto Sei Higuchi Jason C. Mills Rebecca A. Haeusler Domenico Accili |
| author_facet | Wendy M. McKimpson Taiyi Kuo Takumi Kitamoto Sei Higuchi Jason C. Mills Rebecca A. Haeusler Domenico Accili |
| author_sort | Wendy M. McKimpson |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T04:52:07Z |
| format | Article |
| id | doaj.art-2c7263fdf1894364af1e0072aae27e91 |
| institution | Directory Open Access Journal |
| issn | 2772-5723 |
| language | English |
| last_indexed | 2024-04-12T04:52:07Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Gastro Hep Advances |
| spelling | doaj.art-2c7263fdf1894364af1e0072aae27e912022-12-22T03:47:15ZengElsevierGastro Hep Advances2772-57232022-01-0115733745FOXO1 Is Present in Stomach Epithelium and Determines Gastric Cell DistributionWendy M. McKimpson0Taiyi Kuo1Takumi Kitamoto2Sei Higuchi3Jason C. Mills4Rebecca A. Haeusler5Domenico Accili6Division of Endocrinology, Department of Medicine, Columbia University, New York, New York; Naomi Berrie Diabetes Center, Columbia University, New York, New York; Correspondence: Address correspondence to: Wendy M. McKimpson, PhD, Division of Endocrinology, Department of Medicine, Columbia University, Russ Berrie Research Pavilion, 1150 St. Nicholas Ave, Room 234, New York, New York 10032.Division of Endocrinology, Department of Medicine, Columbia University, New York, New York; Naomi Berrie Diabetes Center, Columbia University, New York, New YorkDivision of Endocrinology, Department of Medicine, Columbia University, New York, New York; Naomi Berrie Diabetes Center, Columbia University, New York, New YorkNaomi Berrie Diabetes Center, Columbia University, New York, New York; Department of Pathology and Cell Biology, Columbia University, New York, New YorkSection of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TexasNaomi Berrie Diabetes Center, Columbia University, New York, New York; Department of Pathology and Cell Biology, Columbia University, New York, New YorkDivision of Endocrinology, Department of Medicine, Columbia University, New York, New York; Naomi Berrie Diabetes Center, Columbia University, New York, New YorkBackground 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.http://www.sciencedirect.com/science/article/pii/S2772572322000838Enteroendocrine CellsDiabetes TreatmentCell CycleParietal CellsTranscription Factor |
| spellingShingle | Wendy M. McKimpson Taiyi Kuo Takumi Kitamoto Sei Higuchi Jason C. Mills Rebecca A. Haeusler Domenico Accili FOXO1 Is Present in Stomach Epithelium and Determines Gastric Cell Distribution Gastro Hep Advances Enteroendocrine Cells Diabetes Treatment Cell Cycle Parietal Cells Transcription Factor |
| title | FOXO1 Is Present in Stomach Epithelium and Determines Gastric Cell Distribution |
| title_full | FOXO1 Is Present in Stomach Epithelium and Determines Gastric Cell Distribution |
| title_fullStr | FOXO1 Is Present in Stomach Epithelium and Determines Gastric Cell Distribution |
| title_full_unstemmed | FOXO1 Is Present in Stomach Epithelium and Determines Gastric Cell Distribution |
| title_short | FOXO1 Is Present in Stomach Epithelium and Determines Gastric Cell Distribution |
| title_sort | foxo1 is present in stomach epithelium and determines gastric cell distribution |
| topic | Enteroendocrine Cells Diabetes Treatment Cell Cycle Parietal Cells Transcription Factor |
| url | http://www.sciencedirect.com/science/article/pii/S2772572322000838 |
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