Origin and renewal of goblet cells in the epithelium of the mouse small intestine

Abstract The epithelium of duodenum, jejunum and ileum was investigated in adult female mice given an injection of 3 H‐thymidine and sacrificed at times varying from one hour to 14 days later. The tissues were fixed by perfusion with paraformaldehyde and embedded in Epon. One micron thick sections were cut singly or serially, radioautographed and stained with iron hematoxylin and safranin O. In addition, reconstruction of a crypt was made from serial sections of jejunum. The reconstruction of a crypt shows the well known columnar, goblet, Paneth, and argentaffin cells. There are also little known cell types referred to as oligomucous and granulo‐mucous and pale cells with or without mucus. Of these cells, the only numerous ones are the oligomucous cells, which are located in the lower half of the crypts and contain a few or even only one mucous globule. In the electron microscope, they display long cisterns of rough endoplasmic reticulum parallel to the lateral cell membrane and similar to those observed in goblet cells. In radioautographs of the crypts neither goblet cells, nor Paneth cells, nor argentaffin cells show mitosis or label one hour after 3 H‐thymidine injection. Granulo‐mucous and pale cells are only rarely labeled. In contrast, columnar and oligomucous cells frequently take up label and undergo mitosis. By 12 hours after injection labeled goblet cells have appeared. Since at that time 3 H‐thymidine has left the circulation, the label must have been acquired by transformation of labeled columnar or oligomucous cells. Furthermore, since transitional forms between oligomucous and goblet cells are common, it is concluded that oligomucous cells are those which directly transform into goblet cells. Eventually, like columnar cells, labeled goblet cells migrate to the villus epithelium, climb to the villus tip and fall into the lumen. Although oligomucous cells fit the requirements for goblet cell precursors, not enough of them are labeled to account for the rate of renewal of goblet cells. It is therefore speculated that some undifferentiated columnar cells at the base of the crypts participate in the production of oligomucous cells, which in turn yield goblet cells.