**2. Existence of stem cells in the stomach**

In the stomach, the gastric epithelium is a physiologically self-renewing tissue with a cycle of 2–7 days. Anatomically, the stomach is divided into three main parts: the cardiac region (in humans) or the forestomach (in mice), the main body (corpus), and the distal part (antrum/ pylorus). The mucosa of the stomach is composed of a glandular epithelium with millions of gastric units. Each gland is considered to be monoclonal [1] and is subdivided into the foveolus, isthmus, neck, and bottom regions (**Figure 1**). In the gastric corpus, the glands are long and, from the bottom to the top of the gland, contain zymogenic/chief cells implicated in digestion, parietal cells that are essential for acid production, enterochromaffin-like cells that control acid production, mucous neck cells, and superficial pit cells. In the antrum, the glands are shorter and are composed mainly of mucus-producing cells and enteroendocrine hormone-secreting cells that regulate acid and digestive enzyme production in the corpus. In both regions, some discrete gastric stem cells exist and are instrumental in stomach epithelium renewal under pathophysiological conditions.

**Figure 1.** Architecture of the gastric glands and localization of stem/progenitor cells in the main parts of the stomach. (a) Fundic/corpus gastric gland. (b) Antral/pyloric gastric gland. Stem/progenitor markers identified by lineage tracing are indicated in bold.

In adult organs, tissue stem cells are characterized by self-renewal and asymmetrical division properties, giving rise after mitosis to another stem cell and to a progenitor cell that will undergo expansion and then differentiation into mature cells. These stem cells reside in a physiologically limited and specialized microenvironment, called the niche, which is comprised of cells and extracellular matrices forming the surrounding stroma (including mesenchymal cells, vessels, nerves) and which plays a key role in the maintenance of the stem cell number and functions and in preventing tumorigenesis. The localization of the niche of stem/ progenitor cells varies according to the part of the stomach considered: in the corpus, they are located in the isthmus just below the glandular narrowing, and in the antropyloric region, there are located at the bottom of the glands. Moreover, as is the case in other organs [2], the coexistence of two stem cell populations has been described in the stomach: (1) a population of dividing gastric stem cells recruited under "homeostatic conditions", expressing CD44 or Lgr5 markers and (2) a rare population of quiescent cells recruited mainly upon tissue damage, expressing Villin, Troy, and Mist1 markers (**Figure 1**).
