Elevated stress response marks deeply quiescent reserve cells of gastric chief cells

Abstract Gastrointestinal tract organs harbor reserve cells, which are endowed with cellular plasticity and regenerate functional units in response to tissue damage. However, whether the reserve cells in gastrointestinal tract exist as long-term quiescent cells remain incompletely understood. In the...

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Main Authors: Daisuke Shiokawa, Hiroaki Sakai, Miho Koizumi, Yoshie Okimoto, Yutaro Mori, Yusuke Kanda, Hirokazu Ohata, Hiroaki Honda, Koji Okamoto
Format: Article
Language:English
Published: Nature Portfolio 2023-11-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-023-05550-2
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author Daisuke Shiokawa
Hiroaki Sakai
Miho Koizumi
Yoshie Okimoto
Yutaro Mori
Yusuke Kanda
Hirokazu Ohata
Hiroaki Honda
Koji Okamoto
author_facet Daisuke Shiokawa
Hiroaki Sakai
Miho Koizumi
Yoshie Okimoto
Yutaro Mori
Yusuke Kanda
Hirokazu Ohata
Hiroaki Honda
Koji Okamoto
author_sort Daisuke Shiokawa
collection DOAJ
description Abstract Gastrointestinal tract organs harbor reserve cells, which are endowed with cellular plasticity and regenerate functional units in response to tissue damage. However, whether the reserve cells in gastrointestinal tract exist as long-term quiescent cells remain incompletely understood. In the present study, we systematically examine H2b-GFP label-retaining cells and identify a long-term slow-cycling population in the gastric corpus but not in other gastrointestinal organs. The label-retaining cells, which reside near the basal layers of the corpus, comprise a subpopulation of chief cells. The identified quiescent cells exhibit induction of Atf4 and its target genes including Atf3, a marker of paligenosis, and activation of the unfolded protein response, but do not show elevated expression of Troy, Lgr5, or Mist. External damage to the gastric mucosa induced by indomethacin treatment triggers proliferation of the quiescent Atf4+ population, indicating that the gastric corpus harbors a specific cell population that is primed to facilitate stomach regeneration.
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spelling doaj.art-1b0edcb765b443a8b9fc319beae3f3252023-11-26T14:00:08ZengNature PortfolioCommunications Biology2399-36422023-11-016111010.1038/s42003-023-05550-2Elevated stress response marks deeply quiescent reserve cells of gastric chief cellsDaisuke Shiokawa0Hiroaki Sakai1Miho Koizumi2Yoshie Okimoto3Yutaro Mori4Yusuke Kanda5Hirokazu Ohata6Hiroaki Honda7Koji Okamoto8Division of Molecular Pharmacology, National Cancer Center Research InstituteAdvanced Comprehensive Research Organization, Teikyo UniversityField of Human Disease Models, Major in Advanced Life Sciences and Medicine, Tokyo Women’s Medical UniversityAdvanced Comprehensive Research Organization, Teikyo UniversityAdvanced Comprehensive Research Organization, Teikyo UniversityAdvanced Comprehensive Research Organization, Teikyo UniversityAdvanced Comprehensive Research Organization, Teikyo UniversityField of Human Disease Models, Major in Advanced Life Sciences and Medicine, Tokyo Women’s Medical UniversityAdvanced Comprehensive Research Organization, Teikyo UniversityAbstract Gastrointestinal tract organs harbor reserve cells, which are endowed with cellular plasticity and regenerate functional units in response to tissue damage. However, whether the reserve cells in gastrointestinal tract exist as long-term quiescent cells remain incompletely understood. In the present study, we systematically examine H2b-GFP label-retaining cells and identify a long-term slow-cycling population in the gastric corpus but not in other gastrointestinal organs. The label-retaining cells, which reside near the basal layers of the corpus, comprise a subpopulation of chief cells. The identified quiescent cells exhibit induction of Atf4 and its target genes including Atf3, a marker of paligenosis, and activation of the unfolded protein response, but do not show elevated expression of Troy, Lgr5, or Mist. External damage to the gastric mucosa induced by indomethacin treatment triggers proliferation of the quiescent Atf4+ population, indicating that the gastric corpus harbors a specific cell population that is primed to facilitate stomach regeneration.https://doi.org/10.1038/s42003-023-05550-2
spellingShingle Daisuke Shiokawa
Hiroaki Sakai
Miho Koizumi
Yoshie Okimoto
Yutaro Mori
Yusuke Kanda
Hirokazu Ohata
Hiroaki Honda
Koji Okamoto
Elevated stress response marks deeply quiescent reserve cells of gastric chief cells
Communications Biology
title Elevated stress response marks deeply quiescent reserve cells of gastric chief cells
title_full Elevated stress response marks deeply quiescent reserve cells of gastric chief cells
title_fullStr Elevated stress response marks deeply quiescent reserve cells of gastric chief cells
title_full_unstemmed Elevated stress response marks deeply quiescent reserve cells of gastric chief cells
title_short Elevated stress response marks deeply quiescent reserve cells of gastric chief cells
title_sort elevated stress response marks deeply quiescent reserve cells of gastric chief cells
url https://doi.org/10.1038/s42003-023-05550-2
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