Department of Biomedical Genetics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Department of Biology, University of Rochester, 252 Elmwood Avenue, Rochester, NY 14627, USA.
Stem Cell Reports. 2020 Feb 11;14(2):226-240. doi: 10.1016/j.stemcr.2020.01.003. Epub 2020 Feb 6.
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.
从自我更新的常驻干细胞中产生终末分化细胞对于维持适当的组织架构和生理功能至关重要，尤其是在高周转率的组织中。然而，大多数组织中精确调节细胞过渡和分化的转录网络仍知之甚少。在这里，我们鉴定了 Sox100B，一种果蝇 Sox E 家族转录因子，作为成体肠道干细胞分化的关键调节因子。Sox100B 在干细胞和祖细胞中表达，并需要将肠母细胞祖细胞分化为吸收性肠细胞。从机制上讲，Sox100B 调节另一个关键干细胞分化因子 Sox21a 的表达。支持 Sox100B 对 Sox21a 的直接控制，我们鉴定了 Sox21a 内含子增强子，该增强子在所有肠道祖细胞中均具有活性，并受 Sox100B 直接调节。总之，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分化和增殖以及维持肠道组织稳态至关重要。
