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, eleven cell types have been identified and enumerated (Karam and Leblond: Anat. Rec. 232:231-246, 1992). The dynamics of these cells will be examined in a series of five articles, of which this is the first. This article focuses on the proliferative ability of the cells, as measured by the labeling index in radioautographs from mice sacrificed 30 min after an intravenous injection of H-3-thymidine. Furthermore, the ultrastructure of the cells found to be proliferative was examined in the hope of finding features characteristic of stem cells. On the basis of their labeling index, the epithelial cells have been classified into four groups. The first includes three cell types which do not take up any label and accordingly are non-dividing: parietal or oxyntic cells, cells 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 labeled and, therefore, divide only occasionally: zymogenic or chief cells, entero-endocrine cells, and cells named pre-zymogenic cells as they are suspected of being zymogenic cell precursors. The third group includes two cell types which are always labeled at a low degree and, therefore, divide regularly, but at a low rate: surface mucous cells, herein called pit cells, whose labeling index is 0.8%, and mucous neck cells, simply known as neck cells, 1.8%. The final group consists of three immature cell types with high labeling indices indicating a high rate of division: granule-free cells, which are devoid of secretory granules and have the highest labeling index, 32.4%, pre-pit cells, which possess a few dense secretory granules similar to, but smaller than, those in pit cells, 24.6%, and pre-neck cells, with a small number of secretory granules similar to, but smaller than, those in neck cells, 11.3%. These three cell types, as well as pre-parietal cells, are rapidly 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 pre-pit cells. Ultrastructural studies of granule-free cells reveal that they may be subdivided into three subtypes according to their Golgi features: subtype I, which consists of undifferentiated cells in which the Golgi trans face exhibits no prosecretory vesicles; subtype II, named pre-pit cell precursors because the Golgi trans face shows prosecretory vesicles similar to those in pre-pit cells; and subtype III, named pre-neck cell precursors, whose prosecretory vesicles are similar to those in pre-neck cells. On the other hand, pre-parietal cells include three variants that could each arise from a different granule-free subtype: variant I, which has no mucous secretory granules, could arise from the undifferentiated cells; variant II, which possesses dense mucous granules similar to those in pre-pit cells, could come from pre-pit cell precursors; and variant III, which has cored granules as in pre-neck cells, could come from pre-neck cell precursors. Only the undifferentiated granule-free cells have the features expected from stem cells and, therefore, are considered to be the stem cells of the epithelium. A model based on the radioautographic and morphological data (Fig. 17) summarises the filiation of the other immature cell types as follows. The undifferentiated granule-free cells as stem cells reproduce themselves and give rise to three other cell types: 1) the pre-parietal cells lacking secretory granules (i.e., variant 1); 2) the pre-pit cell precursors, which mainly give rise to pre-pit cells, but also yield 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 the succeeding articles.