p21^waf1/cip1 deficiency does not perturb the intestinal crypt stem cell population after massive small bowel resection

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.