You are here

  • Home
  • Archive
  • Volume 67, Issue 9
  • Lrig1+ gastric isthmal progenitor cells restore normal gastric lineage cells during damage recovery in adult mouse stomach

Article Text

Article menu
Download PDFPDF
Stomach
Original article
Lrig1+ gastric isthmal progenitor cells restore normal gastric lineage cells during damage recovery in adult mouse stomach
  1. Eunyoung Choi1,2,3,
  2. Tyler L Lantz4,
  3. Gregory Vlacich5,
  4. Theresa M Keeley6,
  5. Linda C Samuelson6,
  6. Robert J Coffey1,3,7,8,9,
  7. James R Goldenring1,2,7,3,8,
  8. Anne E Powell4
  1. 1 Nashville VA Medical Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
  2. 2 Section of Surgical Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
  3. 3 Epithelial Biology Center, Nashville, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
  4. 4 Department of Biology, Institute of Molecular Biology, University of Oregon, Oregon, USA
  5. 5 Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
  6. 6 Department of Molecular & Integrative Physiology, The University of Michigan, Michigan, USA
  7. 7 Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
  8. 8 Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
  9. 9 Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
  1. Correspondence to Eunyoung Choi, Epithelial Biology Center and Section of Surgical Science Vanderbilt University Medical Center 10425-D MRB IV 2213 Garland Avenue Nashville, TN 37232; eunyoung.choi{at}vanderbilt.edu and Dr Anne E Powell, Department of Biology, Institute of Molecular Biology, University of Oregon 218 Streisinger Hall 1370 Franklin Blvd Eugene, OR 97405; anniep{at}uoregon.edu

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.

  • Lrig1
  • gastric stem/progenitor cell
  • oxyntic atrophy
  • SPEM
  • metaplasia
  • parietal cell

https://doi.org/10.1136/gutjnl-2017-313874

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Footnotes

    • Contributors EC designed and performed experiments, collected and analysed data, assembled, wrote and revised the manuscript. TL performed experiment, collected and analysed data. GV designed and performed experiments, collected and analysed data. TK designed and performed experiments, collected and analysed data. LS designed experiments, analysed data, revised manuscript. RC designed experiments, analysed data and revised manuscript. JG designed experiments, analysed data and revised manuscript. AP designed and performed experiments, collected and analysed data, assembled, wrote and revised the manuscript.

    • 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.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.