DYNAMICS OF EPITHELIAL-CELLS IN THE CORPUS OF THE MOUSE STOMACH .1. IDENTIFICATION OF PROLIFERATIVE CELL-TYPES AND PINPOINTING OF THE STEM-CELL

In a recent study of the corpus epithelium in the mouse stomach, eleve n cell types have been identified and enumerated (Karam and Leblond: A nat. Rec. 232:231-246, 1992). The dynamics of these cells will be exam ined in a series of five articles, of which this is the first. This ar ticle focuses on the proliferative ability of the cells, as measured b y the labeling index in radioautographs from mice sacrificed 30 min af ter an intravenous injection of H-3-thymidine. Furthermore, the ultras tructure of the cells found to be proliferative was examined in the ho pe of finding features characteristic of stem cells. On the basis of t heir labeling index, the epithelial cells have been classified into fo ur groups. The first includes three cell types which do not take up an y label and accordingly are non-dividing: parietal or oxyntic cells, c ells named pre-parietal as they are immature cells suspected of being parietal cell precursors, and the rare caveolated or brush cells. The second group is composed of three cell types which are only rarely lab eled and, therefore, divide only occasionally: zymogenic or chief cell s, entero-endocrine cells, and cells named pre-zymogenic cells as they are suspected of being zymogenic cell precursors. The third group inc ludes two cell types which are always labeled at a low degree and, the refore, divide regularly, but at a low rate: surface mucous cells, her ein called pit cells, whose labeling index is 0.8%, and mucous neck ce lls, simply known as neck cells, 1.8%. The final group consists of thr ee immature cell types with high labeling indices indicating a high ra te of division: granule-free cells, which are devoid of secretory gran ules and have the highest labeling index, 32.4%, pre-pit cells, which possess a few dense secretory granules similar to, but smaller than, t hose in pit cells, 24.6%, and pre-neck cells, with a small number of s ecretory granules similar to, but smaller than, those in neck cells, 1 1.3%. These three cell types, as well as pre-parietal cells, are rapid ly renewed, with the turnover times estimated at 3.0 days for pre-neck and pre-parietal cells and less than 2.6 days for granule-free and pr e-pit cells. Ultrastructural studies of granule-free cells reveal that they may be subdivided into three subtypes according to their Golgi f eatures: subtype I, which consists of undifferentiated cells in which the Golgi trans face exhibits no prosecretory vesicles; subtype II, na med pre-pit cell precursors because the Golgi trans face shows prosecr etory vesicles similar to those in pre-pit cells; and subtype III, nam ed pre-neck cell precursors, whose prosecretory vesicles are similar t o those in pre-neck cells. On the other hand, pre-parietal cells inclu de three variants that could each arise from a different granule-free subtype: variant I, which has no mucous secretory granules, could aris e from the undifferentiated cells; variant II, which possesses dense m ucous granules similar to those in pre-pit cells, could come from pre- pit cell precursors; and variant III, which has cored granules as in p re-neck cells, could come from pre-neck cell precursors. Only the undi fferentiated granule-free cells have the features expected from stem c ells and, therefore, are considered to be the stem cells of the epithe lium. A model based on the radioautographic and morphological data (Fi g. 17) summarises the filiation of the other immature cell types as fo llows. The undifferentiated granule-free cells as stem cells reproduce themselves and give rise to three other cell types: 1) the pre-pariet al cells lacking secretory granules (i.e., variant 1); 2) the pre-pit cell precursors, which mainly give rise to pre-pit cells, but also yie ld the variant II pre-parietal cells; 3) the pre-neck cell precursors, which mainly give rise to pre-neck cells, but also yield the variant III pre-parietal cells. Further differentiation of these immature cell types into the other cells of the corpus epithelium is examined in th e succeeding articles.