Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine V. Unitarian theory of the origin of the four epithelial cell types

Abstract The previous articles of this series provided presumptive evidence that the four main differentiated cell types in the epithelium of the mouse small intestine: villus columnar, mucous, entero‐endocrine, and Paneth cells, originate from the same precursor, the crypt‐base columnar cell. In the present work, direct evidence was obtained in support of this view. It was first found that crypt‐base columnar cells phagocytose non‐viable cells in their vicinity, with the result that a large phagosome appears in the cytoplasm. Such phagosomes were then used as markers to follow the evolution of crypt‐base columnar cells. In normal control animals, a rare crypt‐base columnar cell includes a large phagosome containing Paneth cell remnants. By six hours after injection of two μCi 3 H‐thymidine per g body weight, a fair number of crypt‐base columnar cells include a different type of phagosome containing labeled nucleus and granulefree cytoplasm, which is attributed to phagocytosis of a labeled crypt‐base columnar cell killed by beta‐radiation from the incorporated 3 H‐thymidine. By 12 hours after 3 H‐thymidine injection, phagosomes have appeared in partly differentiated mid‐crypt columnar cells and oligomucous cells; by 18–24 hours, in fully differentiated columnar cells and in Paneth cells; and by 30 hours, in an entero‐endocrine cell. Since phagosomes are first found in crypt‐base columnar cells and only later in the four differentiated cell types, it is concluded that crypt‐base columnar cells transform into cells of these four types and, therefore, behave as the stem cells of the epithelium. The finding of rare epithelial cells containing two different types of secretory material (either mucous globules and entero‐endocrine granules, or mucous globules and Paneth cell granules) confirms that the stem cells are multipotential. These findings support the Unitarian Theory of epithelial cell formation in the small intestine.