潘氏细胞是一类位于小肠隐窝底部，具有旺盛分泌能力的终末分化肠上皮细胞，是肠道干细胞微环境的重要组成部分。目前对电离辐射损伤后潘氏细胞调控其分泌活性并促进肠道干细胞微环境重建的作用机制尚无明确结论。以往研究报道Mist1是调控消化腺上皮细胞分泌活性最重要的转录因子，我们在前期研究中发现肠隐窝内潘氏细胞可特异性表达Mist1，且敲除Mist1后潘氏细胞的分泌能力显著下降，据此我们提出Mist1可以通过调控潘氏细胞的分泌能力促进电离辐射后肠道干细胞微环境重建这一作用机制。本课题将运用多种Mist1基因工程小鼠、流式分选和肠类器官体培养等技术方法来研究这一作用机制中的具体调控环节。本课题的研究结果将有助于深入认识潘氏细胞对正常和辐照损伤后肠道干细胞微环境的调控作用，为发现胃肠道放射损伤救治的新靶点提供理论及实验基础。

Paneth cells (PC) are specialized terminally differentiated intestinal epithelial cells, which are located at the base of crypt of Lieberkuhn's glands and have great and active secretion capacity. However, it remains unclear that how PC change their secretion level and contribute to the regeneration of ISC niche after radiation exposure. Mist1 is the most important transcriptional factor (TF) which regulates the secretion activity of gastrointestinal exocrine epithelial cells. Our existed data show that PC are the only epithelial cell lineage in crypt with Mist1 expression. When Mist1 is knocked out, PC exhibit a significant loss of secretion vesicles in apical surface. According to these discoveries, we hypothesize that regulating Mist1 expression of PC can promote the reconstituion of microenvironment of ISC after radiation exposure. We will employ a series of Mist1 transgenic mouse lines, FACS and enteroid culture to validate this hypothesis. The results would provide us further understanding of the contribution of PC to both physicological and pathological ISC microenvironment, and facilitate the exploration of new therapeutic targets for the treatment of patients with gastrointestinal injury after radiation exposure.