Robust production of terminally differentiated cells from self-renewing resident stem cells is essential to maintain proper tissue architecture and physiological functions, especially in high-turnover tissues. However, the transcriptional networks that precisely regulate cell transition and differentiation are poorly understood in most tissues. Here, we identified Sox100B, a Drosophila Sox E family transcription factor, as a critical regulator of adult intestinal stem cell differentiation. Sox100B is expressed in stem and progenitor cells and required for differentiation of enteroblast progenitors into absorptive enterocytes. Mechanistically, Sox100B regulates the expression of another critical stem cell differentiation factor, Sox21a. Supporting a direct control of Sox21a by Sox100B, we identified a Sox21a intronic enhancer that is active in all intestinal progenitors and directly regulated by Sox100B. Taken together, our results demonstrate that the activity and regulation of two Sox transcription factors are essential to coordinate stem cell differentiation and proliferation and maintain intestinal tissue homeostasis.

从自我更新的驻留干细胞中可靠地产生最终分化的细胞对于维持适当的组织结构和生理功能（特别是在高周转组织中）至关重要。但是，在大多数组织中对精确调节细胞过渡和分化的转录网络了解甚少。在这里，我们确定了果蝇Sox1 00BSox E家族转录因子，作为成人肠道干细胞分化的关键调节剂。Sox100B在干细胞和祖细胞中表达，是分化成成肠祖细胞成吸收性肠细胞所必需的。从机制上讲，Sox100B调节另一个重要的干细胞分化因子Sox21a的表达。为了支持由Sox100B直接控制Sox21a，我们确定了在所有肠道祖细胞中都有活性并由Sox100B直接调节的Sox21a内含子增强剂。两者合计，我们的结果表明，两个Sox转录因子的活性和调节对于协调干细胞的分化和增殖以及维持肠道组织的动态平衡至关重要。