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PMID: 19013146 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

The gastric epithelial progenitor cell niche and differentiation of the zymogenic (chief) cell lineage.

Developmental biology ·Vol. 325 ·No. 1 ·2009-01-01 ·Pages 211-24

Bredemeyer AJ, Geahlen JH, Weis VG, Huh WJ, Zinselmeyer BH, Srivatsan S, Miller MJ, Shaw AS, Mills JC

Abstract

In the mammalian gastrointestinal tract, the cell fate decisions that specify the development of multiple, diverse lineages are governed in large part by interactions of stem and early lineage progenitor cells with their microenvironment, or niche. Here, we show that the gastric parietal cell (PC) is a key cellular component of the previously undescribed niche for the gastric epithelial neck cell, the progenitor of the digestive enzyme secreting zymogenic (chief) cell (ZC). Genetic ablation of PCs led to failed patterning of the entire zymogenic lineage: progenitors showed premature expression of differentiated cell markers, and fully differentiated ZCs failed to develop. We developed a separate mouse model in which PCs localized not only to the progenitor niche, but also ectopically to the gastric unit base, which is normally occupied by terminally differentiated ZCs. Surprisingly, these mislocalized PCs did not maintain adjacent zymogenic lineage cells in the progenitor state, demonstrating that PCs, though necessary, are not sufficient to define the progenitor niche. We induced this PC mislocalization by knocking out the cytoskeleton-regulating gene Cd2ap in Mist1(-/-) mice, which led to aberrant E-cadherin localization in ZCs, irregular ZC-ZC junctions, and disruption of the ZC monolayer by PCs. Thus, the characteristic histology of the gastric unit, with PCs in the middle and ZCs in the base, may depend on establishment of an ordered adherens junction network in ZCs as they migrate into the base.

MeSH Terms
Adaptor Proteins, Signal Transducing/deficiency,metabolism Animals Basic Helix-Loop-Helix Transcription Factors/deficiency,metabolism Cadherins/metabolism Cell Differentiation Cell Lineage Cell Polarity Cell Proliferation Chief Cells, Gastric/cytology,metabolism,ultrastructure Cytoskeletal Proteins/deficiency,metabolism Epithelial Cells/cytology,metabolism,ultrastructure Intercellular Junctions/metabolism,ultrastructure Mice Models, Biological Parietal Cells, Gastric/cytology,metabolism,ultrastructure Protein Binding Protein Transport Stem Cell Niche/cytology,metabolism,ultrastructure Stem Cells/cytology,metabolism,ultrastructure
Chemicals
Adaptor Proteins, Signal Transducing Basic Helix-Loop-Helix Transcription Factors Bhlha15 protein, mouse CD2-associated protein Cadherins Cytoskeletal Proteins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Bredemeyer Andrew J
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Geahlen Jessica H
Weis Victoria G
Huh Won Jae
Zinselmeyer Bernd H
Srivatsan Subhashini
Miller Mark J
Shaw Andrey S
Mills Jason C
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Article Info
Journal
Developmental biology
Abbr.
Dev Biol
ISSN
1095-564X
DOI
10.1016/j.ydbio.2008.10.025
Published
2009-01-01
Epub
2008-00-31
Pages
211-24
Language
English
Region
United States
NLM ID
0372762
PMCID
PMC2634829
Subset
IM
Grants
NCI NIH HHS · T32 CA113275 · United States
NCI NIH HHS · T32 CA009547-22 · United States
NIDDK NIH HHS · R01 DK066428 · United States
NIDDK NIH HHS · R01 DK079798 · United States
NIDDK NIH HHS · K08 DK066062-03 · United States
NIDDK NIH HHS · R01DK06642804 · United States
NIDDK NIH HHS · R01 DK066428-04 · United States
NIDDK NIH HHS · R01 DK079798-01A2 · United States
NIDDK NIH HHS · P30 DK52574 · United States
NIDDK NIH HHS · P30 DK052574-08 · United States
NIDDK NIH HHS · P30 DK052574 · United States
NIDDK NIH HHS · K08 DK066062-05 · United States
NIDDK NIH HHS · R01 DK058366 · United States
NCI NIH HHS · T32 CA009547-21 · United States
NIDDK NIH HHS · K08 DK066062-04 · United States
NIDDK NIH HHS · P30 DK052574-06 · United States
NIDDK NIH HHS · R01 DK058366-08 · United States
NCI NIH HHS · T32 CA009547 · United States
NIDDK NIH HHS · K08 DK066062 · United States
NIDDK NIH HHS · R01DK05836608 · United States
NIDDK NIH HHS · P30 DK052574-07 · United States
External Links
PubMed source DOI: 10.1016/j.ydbio.2008.10.025 PMC Full Text View journal details
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