FOXO1 Is Present in Stomach Epithelium and Determines Gastric Cell Distribution.
Cell Cycle
Diabetes Treatment
Enteroendocrine Cells
Parietal Cells
Transcription Factor
Journal
Gastro hep advances
ISSN: 2772-5723
Titre abrégé: Gastro Hep Adv
Pays: Netherlands
ID NLM: 9918350485906676
Informations de publication
Date de publication:
2022
2022
Historique:
entrez:
19
9
2022
pubmed:
20
9
2022
medline:
20
9
2022
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 36117550
doi: 10.1016/j.gastha.2022.05.005
pmc: PMC9481069
mid: NIHMS1835133
doi:
Types de publication
Journal Article
Langues
eng
Pagination
733-745Subventions
Organisme : NCRR NIH HHS
ID : S10 RR027050
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK057539
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007343
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK063608
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL125649
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK121873
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK094989
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK056338
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK114372
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK064819
Pays : United States
Déclaration de conflit d'intérêts
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.
Références
Cell. 2007 Jan 26;128(2):309-23
pubmed: 17254969
Nature. 2014 Dec 18;516(7531):400-4
pubmed: 25363776
Dev Biol. 2004 Jun 15;270(2):443-54
pubmed: 15183725
Cell. 2019 Feb 21;176(5):1158-1173.e16
pubmed: 30712869
Diabetes Obes Metab. 2007 Nov;9 Suppl 2:140-6
pubmed: 17919188
PLoS Biol. 2018 Dec 10;16(12):e2006249
pubmed: 30532187
Proc Natl Acad Sci U S A. 2021 Nov 9;118(45):
pubmed: 34732569
Cell Stem Cell. 2016 Mar 3;18(3):410-21
pubmed: 26908146
Front Endocrinol (Lausanne). 2019 Apr 26;10:260
pubmed: 31080438
Nature. 1999 Dec 9;402(6762):656-60
pubmed: 10604470
Gastroenterology. 2014 Mar;146(3):754-764.e3
pubmed: 24316261
Nat Genet. 2012 Mar 11;44(4):406-12, S1
pubmed: 22406641
Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2975-80
pubmed: 14978268
Cell Stem Cell. 2020 Jun 4;26(6):910-925.e6
pubmed: 32243780
Dev Biol. 2018 Mar 15;435(2):97-108
pubmed: 29339095
Nat Protoc. 2012 Sep;7(9):1728-40
pubmed: 22936215
Cell Metab. 2005 Sep;2(3):153-63
pubmed: 16154098
Mol Cell Biol. 2009 Aug;29(16):4417-30
pubmed: 19506018
Methods Mol Biol. 2017;1597:217-228
pubmed: 28361321
Nat Commun. 2014 Jun 30;5:4242
pubmed: 24979718
J Diabetes Investig. 2017 Nov;8(6):726-734
pubmed: 28267275
Am J Anat. 1982 Jul;164(3):187-207
pubmed: 7124652
Cell. 2017 Nov 2;171(4):824-835.e18
pubmed: 29056338
Br J Pharmacol. 1973 Feb;47(2):415-21
pubmed: 4722050
Gastroenterology. 2007 Dec;133(6):1989-98
pubmed: 18054570
Nature. 2000 Apr 13;404(6779):782-7
pubmed: 10783894
FEBS J. 2014 Oct;281(19):4421-38
pubmed: 25065674
Genes Dev. 2002 Jun 15;16(12):1488-97
pubmed: 12080087
Diabetologia. 2010 Apr;53(4):699-711
pubmed: 20033803
Nat Protoc. 2011 Nov 10;6(12):1920-8
pubmed: 22082986
Endocrinology. 2012 Dec;153(12):5782-95
pubmed: 23064014
J Biol Chem. 2007 Oct 12;282(41):30107-19
pubmed: 17711846
Genesis. 2007 Sep;45(9):593-605
pubmed: 17868096
Dev Cell. 2003 Jan;4(1):119-29
pubmed: 12530968
Cell Rep. 2014 Mar 27;6(6):1046-1058
pubmed: 24613355
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Ann Oncol. 2001;12 Suppl 2:S63-8
pubmed: 11762354
Nat Genet. 2002 Oct;32(2):245-53
pubmed: 12219087
Mol Cell. 2010 May 28;38(4):576-89
pubmed: 20513432
Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4471-6
pubmed: 15070742
Nature. 2007 Oct 25;449(7165):1003-7
pubmed: 17934449
J Biol Chem. 2019 Aug 30;294(35):13106-13116
pubmed: 31308176
Development. 2007 Feb;134(3):427-38
pubmed: 17185316
Cell. 2004 Apr 16;117(2):211-23
pubmed: 15084259
J Biol Chem. 2019 Jul 5;294(27):10438-10448
pubmed: 31118273
Curr Protoc Bioinformatics. 2014 Sep 08;47:11.12.1-34
pubmed: 25199790
Mol Cell Biol. 2000 Dec;20(24):9138-48
pubmed: 11094066
Nucleic Acids Res. 2012 Dec;40(22):11499-509
pubmed: 23066095
Int Immunol. 2008 May;20(5):671-81
pubmed: 18375530
Endocrinology. 2012 Jul;153(7):3054-65
pubmed: 22685263
Gastroenterology. 2015 Jan;148(1):126-136.e6
pubmed: 25307862
Nature. 2017 Nov 16;551(7680):333-339
pubmed: 29144463
Diabetes. 2013 Jan;62(1):183-93
pubmed: 22933109
J Clin Invest. 2002 Dec;110(12):1839-47
pubmed: 12488434
J Biol Chem. 2005 May 27;280(21):20589-95
pubmed: 15788402
Nature. 2017 Jan 12;541(7636):182-187
pubmed: 28052057
Proc Natl Acad Sci U S A. 2019 Oct 1;116(40):20033-20042
pubmed: 31527256