Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine I. Columnar cell

Abstract The columnar cells, i.e., the cells which contain neither mucous globules, nor entero‐endocrine granules, nor Paneth type secretion, were investigated independently of other cells in duodenum, jejunum and ileum using light and electron microscopy as well as radioautography in mice sacrificed at various times after single injection or continuous infusion of 3 H‐thymidine. The columnar cells exhibit local differences allowing their classification into four sub‐groups: (a) The crypt‐base columnar cells are immature proliferative cells occupying the nine lowest cell positions of the crypt on the average. (b) The mid‐crypt columnar cells occupy the next positions up to 19 in ileum and 27 elsewhere; they proliferate and show features gradually changing from undifferentiated ones near the base to partially differentiated ones higher up. (c) The crypt‐top columnar cells occupy the rest of the crypt; they do not divide but they continue to differentiate. (d) Finally, the villus columnar cells are fully differentiated absorptive cells. Cryp‐base and mid‐crypt columnar cells take up 3 H‐thymidine label prior to division. With time after a 3 H‐thymidine injection, the intensity of their labeling decreases, while heavily labeled columnar cells appear in crypt‐top by six hours and on the villus by 12 and more hours. Hence, columnar cells migrate. The migration is associated with gradual differentiation from the immature crypt‐base columnar cells to the mature villus columnar cells. The latter eventually reach the villus tips where they drop into the lumen. The columnar cells constitute a large majority of the epithelial cells (95, 94 and 89% in duodenum, jejunum and ileum, respectively). Hence, they are likely to play a key role in the renewal of the epithelium in the three regions of the small intestine. The turnover time of columnar cells estimated from results of continuous 3 H‐thymidine infusion is 3.3 days in duodenum and 3.4 days in jejunum. Evidence from turnover time data indicates that the mitoses of columnar cells produce more cells than required for their own renewal. Presumably some of the mitoses give rise to cells of a type other than columnar.