@article{23204c1ff0fd4d3e878fbfc0bd0a3f1a,
title = "Lrig1+ gastric isthmal progenitor cells restore normal gastric lineage cells during damage recovery in adult mouse stomach",
abstract = "Objective Lrig1 is a marker of proliferative and quiescent stem cells in the skin and intestine. We examined whether Lrig1-expressing cells are long-lived gastric progenitors in gastric glands in the mouse stomach. We also investigated how the Lrig1-expressing progenitor cells contribute to the regeneration of normal gastric mucosa by lineage commitment to parietal cells after acute gastric injury in mice. Design We performed lineage labelling using Lrig1-CreERT2/+;R26R-YFP/+ (Lrig1/YFP) or R26R-LacZ/+ (Lrig1/LacZ) mice to examine whether the Lrig1-YFP-marked cells are gastric progenitor cells. We studied whether Lrig1-YFP-marked cells give rise to normal gastric lineage cells in damaged mucosa using Lrig1/YFP mice after treatment with DMP-777 to induce acute injury. We also studied Lrig1-CreERT2/CreERT2 (Lrig1 knockout) mice to examine whether the Lrig1 protein is required for regeneration of gastric corpus mucosa after acute injury. Results Lrig1-YFP-marked cells give rise to gastric lineage epithelial cells both in the gastric corpus and antrum, in contrast to published results that Lgr5 only marks progenitor cells within the gastric antrum. Lrig1-YFP-marked cells contribute to replacement of damaged gastric oxyntic glands during the recovery phase after acute oxyntic atrophy in the gastric corpus. Lrig1 null mice recovered normally from acute gastric mucosal injury indicating that Lrig1 protein is not required for lineage differentiation. Lrig1+ isthmal progenitor cells did not contribute to transdifferentiating chief cell lineages after acute oxyntic atrophy. Conclusions Lrig1 marks gastric corpus epithelial progenitor cells capable of repopulating the damaged oxyntic mucosa by differentiating into normal gastric lineage cells in mouse stomach.",
keywords = "Lrig1, SPEM, gastric stem/progenitor cell, metaplasia, oxyntic atrophy, parietal cell",
author = "Eunyoung Choi and Lantz, {Tyler L.} and Gregory Vlacich and Keeley, {Theresa M.} and Samuelson, {Linda C.} and Coffey, {Robert J.} and Goldenring, {James R.} and Powell, {Anne E.}",
note = "Funding Information: Funding these studies were supported by grants from a Department of Veterans affairs Merit review award (i01BX000930) and niH rO1 DK071590, as well as a grant from the Martell Foundation (to Jrg), niH r01 ca163563, r01 ca46413 and gi Special Program of research excellence P50 95 103 (to rJc), niH K01 DK103737, a research Scholar award from the american gastroenterological association (to aeP) and niH P01-DK06041 (to lcS). this work was supported by core resources of the Vanderbilt Digestive Disease center (P30 DK058404) and the Vanderbilt-ingram cancer center (P30 ca68485), and imaging was supported by both the Vanderbilt combined imaging Shared resource and the Vanderbilt Digital Histology Shared resource. Funding Information: 4Department of Biology, institute of Molecular Biology, University of Oregon, Oregon, USa 5Department of radiation Oncology, Vanderbilt University School of Medicine, nashville, tennessee, USa 6Department of Molecular & integrative Physiology, the University of Michigan, Michigan, USa 7Department of Medicine, Vanderbilt University School of Medicine, nashville, tennessee, USa 8Department of cell and Developmental Biology, Vanderbilt University School of Medicine, nashville, tennessee, USa 9Vanderbilt-ingram cancer center, Vanderbilt University School of Medicine, nashville, tennessee, USa Acknowledgements these studies were supported by grants from a Department of Veterans affairs Merit review award (i01BX000930) and niH rO1 DK071590, as well as a grant from the Martell Foundation (to J.r.g.), niH r01 ca163563, r01 ca46413 and gi Special Program of research excellence P50 95103 (to r.J.c), niH K01 DK103737, a research Scholar award from the american gastroenterological association (to a.e.P.), and niH P01-DK06041 (to l.c.S). this work was supported by core resources of the Vanderbilt Digestive Disease center (P30 DK058404), the Vanderbilt-ingram cancer center (P30ca68485), and imaging supported by both the Vanderbilt combined imaging Shared resource and the Vanderbilt Digital Histology Shared resource. Publisher Copyright: {\textcopyright} 2018 Article author(s).",
year = "2018",
month = sep,
day = "1",
doi = "10.1136/gutjnl-2017-313874",
language = "English",
volume = "67",
pages = "1595--1605",
journal = "Gut",
issn = "0017-5749",
number = "9",
}