The stem-cell zone of the small intestinal epithelium. III. Evidence from columnar, enteroendocrine, and mucous cells in the adult mouse.

In the first two articles of this series we demonstrated restriction of Paneth cell formation to positions 5 and above. Restriction was independent of the Paneth cell population-density gradient in the crypt base. We concluded that our results were consistent with the presence in the adult of a stem-cell zone in positions 1-4 in which stem cells received no inducement to differentiate. To further test the stem-cell zone hypothesis we determined the site of stem-cell differentiation along mucous, enteroendocrine, and columnar cell lines using radioautography with 3H-thymidine as a label. One hour after injection of 3H-thymidine, labeled mucous cells were not observed below position 5. Only later did they appear in lower positions and not until 4 days after injection were they observed in position 1. Labeled enteroendocrine cells first appeared above, and then were seen in the top of, and finally in the middle and bottom of the Paneth cell distribution. Thirty hours after injection there were two populations of labeled columnar cells in the crypt base, a heavily labeled population and a lightly labeled one. At this time interval the heavily labeled columnar cells were only observed in positions 5 and above, but they appeared in positions 1-4 by 66 hours after injection. The above evidence led us to conclude that all differentiated offspring of the common epithelial stem cell originate in positions 5 and above. Most columnar, mucous, and enteroendocrine cells originating in positions 5 and above migrate upward. However some of these cells migrate down. All differentiated cells found in positions 1-4 migrated down from their origin in position 5 or above. We also found that only stem cells proliferate in positions 1-4. We concluded that in the adult, there is a stem-cell zone in positions 1-4 where stem cells are not induced to differentiate and persist as stem cells throughout life.