ATF4 marks quiescent reserve cells of gastric chief cells

Hierarchically organized tissues, such as hematopoietic systems, muscle, or skin harbor deeply quiescent stem cells which start proliferating in response to external insults. In contrast, it remains obscure whether similar quiescent cells exist in epithelia of digestive organs. Here we identified a deeply quiescent population in gastric corpus but not in other gastrointestinal organs after systematic examination of H2b-GFP label-retaining cells. The label-retaining cells in corpus epithelia belonged to a subpopulation of chief cells that were located near basal layers of corpus and did not overlap with Troyhigh, Lgr5high, or Misthigh cell population. The identified quiescent cells were marked with activation of Atf4 and unfolded protein response. External damages by indomethacin treatment triggered proliferation of the quiescent populations, indicating that chief cells of gastric corpus harbor deeply quiescent reserve cells with high levels of internal stress response activity. Stomach epithelial cells of the H2b-GFP mice were isolated by Fluorescence-activated cell sorting (FACS) according to Epcam-PE and GFP signals and analyzed using scRNAseq.