1 Children's Health Research Institute, Western University , London, Canada .
Stem Cells Dev. 2013 Nov 15;22(22):2935-43. doi: 10.1089/scd.2013.0106. Epub 2013 Aug 2.
Progenitor expansion during development is a highly regulated process dictating the final organ size, while expansion of specific progenitor populators can adjust the final cellular composition of the organ. Understanding factors involved in these pathways is required to develop cell-based therapies such as β-cell transplantation for conditions such as diabetes mellitus. One versatile factor controlling both processes as well as a network of other proteins involved in pancreatic and duodenal development is the transcription factor SOX9. This review will focus on a comparison of SOX9 function during progenitor expansion and differentiation in the developing pancreas and duodenum with specific focus on endocrine development. During human pancreatic development, SOX9 functions in a dose-dependent manner to regulate epithelial progenitor expansion and endocrine differentiation. SOX9 expression is eventually limited to a subset of ductal and centroacinar cells, hypothesized to be the pancreatic stem cell compartment. Similarly, during duodenal development, SOX9 is expressed in most early epithelial progenitors and becomes gradually restricted to proliferative progenitors in the lower crypts, as well as mature Paneth and enteroendocrine cells indicating some differences in functional roles. However, in both developmental contexts, SOX9 is involved in pathways responsible for cellular proliferation and differentiation, such as Notch and Wnt. With its adaptable and central function in progenitor control, SOX9 represents an attractive target for manipulation for in vitro progenitor expansion and differentiation meriting further investigation.
在发育过程中，祖细胞的扩增是一个高度受调控的过程，决定着最终器官的大小，而特定祖细胞群体的扩增可以调整器官的最终细胞组成。了解这些途径中涉及的因素对于开发基于细胞的治疗方法（如用于糖尿病的β细胞移植）是必要的。转录因子 SOX9 是一种多功能因子，它可以控制这两个过程以及参与胰腺和十二指肠发育的其他蛋白质网络。这篇综述将重点比较 SOX9 在发育中的胰腺和十二指肠祖细胞扩增和分化过程中的功能，特别关注内分泌发育。在人类胰腺发育过程中，SOX9 以剂量依赖的方式调节上皮祖细胞的扩增和内分泌分化。SOX9 的表达最终局限于导管和中央腺细胞的一个亚群，这被假设为胰腺干细胞区室。同样，在十二指肠发育过程中，SOX9 在大多数早期上皮祖细胞中表达，并逐渐局限于下部隐窝中的增殖祖细胞以及成熟的 Paneth 和肠内分泌细胞，表明其功能作用存在一些差异。然而，在这两种发育背景下，SOX9 都参与了负责细胞增殖和分化的途径，如 Notch 和 Wnt。SOX9 作为祖细胞控制的一种适应性和核心功能，代表了用于体外祖细胞扩增和分化的有吸引力的操作靶点，值得进一步研究。
