Chief cell plasticity is the origin of metaplasia following acute injury in the stomach mucosa.
gastric epithelial cell function
gastric metaplasia
mucosal injury
Journal
Gut
ISSN: 1468-3288
Titre abrégé: Gut
Pays: England
ID NLM: 2985108R
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
03
06
2021
accepted:
31
08
2021
pubmed:
10
9
2021
medline:
10
5
2022
entrez:
9
9
2021
Statut:
ppublish
Résumé
Metaplasia arises from differentiated cell types in response to injury and is considered a precursor in many cancers. Heterogeneous cell lineages are present in the reparative metaplastic mucosa with response to injury, including foveolar cells, proliferating cells and spasmolytic polypeptide-expressing metaplasia (SPEM) cells, a key metaplastic cell population. Zymogen-secreting chief cells are long-lived cells in the stomach mucosa and have been considered the origin of SPEM cells; however, a conflicting paradigm has proposed isthmal progenitor cells as an origin for SPEM. Gastric intrinsic factor (GIF) is a stomach tissue-specific gene and exhibits protein expression unique to mature mouse chief cells. We generated a novel chief cell-specific driver mouse allele, GIF-rtTA. GIF-GFP reporter mice were used to validate specificity of GIF-rtTA driver in chief cells. GIF-Cre-RnTnG mice were used to perform lineage tracing during homoeostasis and acute metaplasia development. L635 treatment was used to induce acute mucosal injury and coimmunofluorescence staining was performed for various gastric lineage markers. We demonstrated that mature chief cells, rather than isthmal progenitor cells, serve as the predominant origin of SPEM cells during the metaplastic process after acute mucosal injury. Furthermore, we observed long-term label-retaining chief cells at 1 year after the GFP labelling in chief cells. However, only a very small subset of the long-term label-retaining chief cells displayed the reprogramming ability in homoeostasis. In contrast, we identified chief cell-originating SPEM cells as contributing to lineages within foveolar cell hyperplasia in response to the acute mucosal injury. Our study provides pivotal evidence for cell plasticity and lineage contributions from differentiated gastric chief cells during acute metaplasia development.
Identifiants
pubmed: 34497145
pii: gutjnl-2021-325310
doi: 10.1136/gutjnl-2021-325310
pmc: PMC8901801
mid: NIHMS1757366
doi:
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1068-1077Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK101332
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK058404
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA244970
Pays : United States
Organisme : NIDDK NIH HHS
ID : F32 DK111101
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA236733
Pays : United States
Organisme : NIDDK NIH HHS
ID : F31 DK117592
Pays : United States
Organisme : NCI NIH HHS
ID : K25 CA204599
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK121869
Pays : United States
Organisme : BLRD VA
ID : I01 BX000930
Pays : United States
Informations de copyright
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
Références
Gut. 2012 Dec;61(12):1678-85
pubmed: 22198711
Gastroenterology. 2020 May;158(6):1650-1666.e15
pubmed: 32032583
Nat Cell Biol. 2017 Jul;19(7):774-786
pubmed: 28581476
J Pathol. 2018 Jun;245(2):132-137
pubmed: 29508389
Lab Invest. 1999 Jun;79(6):639-46
pubmed: 10378506
EMBO J. 2018 Apr 3;37(7):
pubmed: 29467218
Gastroenterology. 2018 Mar;154(4):839-843.e2
pubmed: 29248442
Exp Cell Res. 2011 Nov 15;317(19):2759-64
pubmed: 21907708
Cell Mol Gastroenterol Hepatol. 2016 May 17;2(5):605-624
pubmed: 27990460
Gastroenterology. 2008 Feb;134(2):511-22
pubmed: 18242217
J Pathol. 1993 Sep;171(1):3-4
pubmed: 8229453
Cancer Epidemiol Biomarkers Prev. 2012 May;21(5):709-19
pubmed: 22374991
Cell Mol Gastroenterol Hepatol. 2019;7(1):251-253.e1
pubmed: 30585163
Gastroenterology. 2020 Feb;158(3):598-609.e5
pubmed: 31589873
Cell Mol Gastroenterol Hepatol. 2022;13(1):199-217
pubmed: 34455107
Anat Rec. 1993 Jun;236(2):297-313
pubmed: 8338234
Nat Rev Mol Cell Biol. 2007 May;8(5):369-78
pubmed: 17377526
Gastroenterology. 2010 Dec;139(6):2018-2027.e2
pubmed: 20708616
Cell Mol Gastroenterol Hepatol. 2016 Nov 16;3(1):11-26
pubmed: 28174755
Cell Mol Gastroenterol Hepatol. 2020;9(1):61-78
pubmed: 31473306
Am J Physiol Gastrointest Liver Physiol. 2017 Jan 1;312(1):G67-G76
pubmed: 27881402
Am J Pathol. 1993 Mar;142(3):663-8
pubmed: 7681255
Cell Mol Gastroenterol Hepatol. 2019;8(3):379-405
pubmed: 31071489
Gastroenterology. 2010 Dec;139(6):2028-2037.e9
pubmed: 20854822
J Physiol. 2018 Sep;596(17):3861-3867
pubmed: 29427515
Cell Mol Gastroenterol Hepatol. 2017 Mar 23;4(1):85-88
pubmed: 28560292
PLoS Pathog. 2017 Oct 5;13(10):e1006573
pubmed: 28982167
Nat Rev Cancer. 2017 Oct;17(10):594-604
pubmed: 28860646
Gastroenterology. 2017 Mar;152(4):762-766.e7
pubmed: 27932312
CA Cancer J Clin. 2012 Sep-Oct;62(5):283-98
pubmed: 22987332
Nat Rev Gastroenterol Hepatol. 2018 May;15(5):257-273
pubmed: 29463907
Lancet Oncol. 2012 Jun;13(6):607-15
pubmed: 22575588
Gastroenterology. 2016 Apr;150(4):918-30.e13
pubmed: 26677984
Gastroenterology. 2004 Aug;127(2):582-94
pubmed: 15300590
Nat Rev Gastroenterol Hepatol. 2017 May;14(5):296-304
pubmed: 28270694
Dis Model Mech. 2018 Jul 23;11(7):
pubmed: 30037967
Cell Mol Gastroenterol Hepatol. 2017 Mar 06;4(1):89-94
pubmed: 28560293
Cancer Cell. 2015 Dec 14;28(6):800-814
pubmed: 26585400
Am J Physiol Gastrointest Liver Physiol. 2018 May 1;314(5):G583-G596
pubmed: 29345968
Cell. 2013 Oct 10;155(2):357-68
pubmed: 24120136