Abstract
Abdominal irradiation causes damage and loss of intestinal epithelium that requires proliferation of surviving stem cells for regeneration. Evidence for this role of stem cells is indirect due to lack of stem cell biomarkers. This study tested the hypothesis that SOX9 marks proliferating stem cells after irradiation and that insulin‐like growth factor I (IGF‐I) promotes survival or expansion of SOX9 positive cells.Wild type or SOX9‐GFP mice were killed 1 through 9 days after 14Gy of abdominal irradiation and intestines collected. Morphology was assessed by H&E. Immunofluorescence for SOX9 and Ki67 and visualization of SOX9‐GFP tested if SOX9 marked proliferating microcolonies or regenerating crypts. Effects of IGF‐I on SOX9 were evaluated by immunoblot.There was almost complete loss of small intestinal crypts and damage to colon epithelium by days 3‐5 after irradiation. Hyperplastic regenerating crypts were observed on days 5‐9. SOX9‐GFP marked and SOX9 co‐localized with Ki67 in microcolonies and hyperplastic, regenerating intestinal crypts. IGF‐1 treatment increased SOX9 protein levels.SOX9 provides a new biomarker of putative stem cells in microcolonies and regenerating crypts in the intestine after irradiation. The SOX9‐GFP reporter mouse provides a useful model to evaluate stem cell survival and expansion, and effects of trophic therapies during regeneration after irradiation.NIH DK40247‐16
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