Abstract
The murine intestine, like that of other mammalians, continues to develop after birth until weaning; however, whether this occurs in response to an intrinsic developmental program or food intake remains unclear. Here, we report a novel system for the allotransplantation of small intestine and colon harvested from Lgr5EGFP-IRES-CreERT2/+; Rosa26rbw/+ mice immediately after birth into the subrenal capsule of wild-type mice. By histological and immunohistochemical analysis, the developmental process of transplanted small intestine and colon was shown to be comparable with that of the native tissues: mature intestines equipped with all cell types were formed, indicating that these organs do not require food intake for development. The intestinal stem cells in transplanted tissues were shown to self-renew and produce progeny, resulting in the descendants of the stem cells occupying the crypt-villus unit of the small intestine or the whole crypt of the colon. Collectively, these findings indicate that neonatal intestine development follows an intrinsic program even in the absence of food stimuli.
Highlights
The murine intestine, like that of other mammalians, continues to develop after birth until weaning; whether this occurs in response to an intrinsic developmental program or food intake remains unclear
Lgr5+ cells appeared in the crypts at P5, and the number per crypt significantly increased at postnatal day 14 (P14) compared with P5 (Fig. 1g,g’; Supplementary Fig. 1j,j’,n,n’, Fig. 1j,j’, Supplementary Fig. 2c)[7, 9, 10]
Neonatal small intestine differentiation analyses revealed Periodic acid-Schiff (PAS)-stained goblet cells and alkaline phosphatase (ALP)+ enterocytes at P1 (Supplementary Fig. 1c,d,g,h,k,l,o,p) and villus sucrose-isomaltase (SIM)—a marker for mature brush border—starting at P10, which later expanded throughout the entire villus (Fig. 1h; Supplementary Fig. 1q,q’; Fig. 1k)
Summary
The murine intestine, like that of other mammalians, continues to develop after birth until weaning; whether this occurs in response to an intrinsic developmental program or food intake remains unclear. Intestinal tissues experience dynamic changes both in their structure and in the mechanisms of digestion and absorption, at birth and at weaning[1] External factors such as food intake may be involved in the maturation of intestines; internal factors are considered the dominant players in the maturation process. Several reports have supported this concept, establishing techniques for the transplantation of rat small intestines into the anterior chamber[2] or subrenal capsule[3], where the effects of digestion need not be considered It remains to be definitively confirmed whether the transplanted intestines proliferate in a stem cell-dependent manner as in the case of native tissues. The autonomous construction of self-contained intestinal tissues independently of food intake and the subsequent influences of digestion
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