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

Author:

Shiokawa Daisuke,Sakai Hiroaki,Koizumi Miho,Okimoto Yoshie,Mori Yutaro,Kanda Yusuke,Ohata Hirokazu,Honda HiroakiORCID,Okamoto KojiORCID

Abstract

AbstractGastrointestinal 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.

Funder

MEXT | Japan Science and Technology Agency

MEXT | Japan Society for the Promotion of Science

Princess Takamatsu Cancer Research Fund The vehicle racing commemorative foundation National cancer center Japan

Publisher

Springer Science and Business Media LLC

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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