The life history of cells in renewing systems

Abstract Cell populations may be classified into three groups: static , which do not divide in the adult (e.g., neurons), expanding , which may divide but at a decreasing rate with age (e.g., kidney cells), and renewing , which undergo active division throughout life (e.g., blood cells, intestinal and seminiferous epithelium). The first two groups consist of nonrenewing populations whose cells usually survive as long as the body itself. In contrast, the cells of renewing populations have a short life, of the order of 2 to 3 days in the intestinal epithelium of rodents and 7 to 8 weeks in their seminiferous epithelium. In the present work, the life of a nonrenewing cell—the proximal convoluted tubule cell of kidney—is compared to that of the renewing cells of small intestine and testis. The proximal convoluted tubule cell arises during embryonic development, when it has few organelles, many free ribosomes, a pale nucleus with diffuse chromatin, and a large open‐network nucleolus. As the cell differentiates, organelles accumulate while free ribosomes decrease in number, chromatin masses appear in the nucleus, and the nucleolus becomes rather dense. With old age, some of the cells show features interpreted as senescence, particularly a small dense nucleolus. The short‐lived columnar cells of small intestine in adult rats arise from stem cells present in the base of the crypts. These cells have features similar to those of the embryonic proximal tubule cell, particularly many free ribosomes and a large open‐network nucleolus. The stem cells give rise to cells which ascend crypts and villi. Shortly after the cells reach the villus, they acquire a full set of organelles, suggesting maturity, while free ribosomes decrease in number and the nucleolus undergoes condensation. Meanwhile radioautographic tests indicate that the production by the cells of glycoproteins identified as intestinal enzymes reaches a high level. However, when cells arrive in the villus tip region, their activity decreases, as shown by reduced enzyme production, while the nucleolus appears atrophic. The cells are then lost to the lumen. The cells of the seminiferous epithelium also arise in the adult from stem cells with embryonic features. In the course of a complex differentiation, the nucleolus becomes atrophic and disappears. Soon thereafter the fragile spermatozoon stage is reached. Thus, the renewing cells of the adult show in rapid succession some of the features occurring slowly during the life of nonrenewing cells: origin from embryonic‐like elements, maturation, and senescence indicated by a fragile state before life's end.