P21 waf1/cip1 deficiency does not perturb the intestinal crypt stem cell population after massive small bowel resection

Abstract

Background After small bowel resection (SBR), adaptation is initiated in intestinal crypts where stem cells reside. Prior studies revealed SBR-induced enterocyte proliferation requires the expression of p21 waf1/cip1. As deficient expression of p21 waf1/cip1 has been shown to result in reduced numbers of hematopoietic stem cells. We sought to test the hypothesis that p21 waf1/cip1deficiency similarly perturbs the intestinal stem cell population after SBR. Methods Control ( n = 21; C57Bl/6) and p21 waf1/cip1-null mice ( n = 30) underwent 50% proximal SBR or sham operation. After 3 days, the ileum was harvested and the crypt stem cell population evaluated by counting crypt base columnar cells on histologic sections, determining the expression of Musashi-1 and Lgr5, and profiling the transcriptional expression of 84 known stem cell genes. Results There were no significant differences in crypt base columnar cells, expression of Musashi-1 or Lgr5, or in stem cell gene expression after SBR in control mice. Furthermore, there were no differences in these markers between controls and p21 waf1/cip1-null mice. Conclusion In contrast with bone marrow stem cells, the stem cell population of the gut is unaffected by deficient expression of p21 waf1/cip1. Additional mechanisms for the role of p21 waf1/cip1 in small bowel proliferation and adaptation after massive SBR must be considered.