Department of Molecular Medicine, Mayo Clinic, College of Medicine, 200 First St. SW, Rochester, MN, 55905, USA.
Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, National Clinical Research Center for Metabolic Diseases, 139 Middle Renmin Road, Changsha, Hunan Province, 410013, China.
Stem Cell Res Ther. 2017 Nov 2;8(1):240. doi: 10.1186/s13287-017-0694-z.
Transcription factors regulate gene expression through binding to specific enhancer sequences. Pancreas/duodenum homeobox protein 1 (PDX1), Neurogenin-3 (NEUROG3), and V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA) are transcription factors critical for beta cell development and maturation. NEUROG3 is expressed in endocrine progenitor cells and controls islet differentiation and regeneration. PDX1 is essential for the development of pancreatic exocrine and endocrine cells including beta cells. PDX1 also binds to the regulatory elements and increases insulin gene transcription. Likewise, MAFA binds to the enhancer/promoter region of the insulin gene and drives insulin expression in response to glucose. In addition to those natural roles in beta cell development and maturation, ectopic expression of PDX1, NEUROG3, and/or MAFA has been successfully used to reprogram various cell types into insulin-producing cells in vitro and in vivo, such as pancreatic exocrine cells, hepatocytes, and pluripotent stem cells. Here, we review biological properties of PDX1, NEUROG3, and MAFA, and their applications and limitations for beta cell regenerative approaches. The primary source literature for this review was acquired using a PubMed search for articles published between 1990 and 2017. Search terms include diabetes, insulin, trans-differentiation, stem cells, and regenerative medicine.
转录因子通过与特定的增强子序列结合来调节基因表达。胰腺/十二指肠同源盒蛋白 1（PDX1）、神经生成素 3（NEUROG3）和 v-maf 肌肉腱膜纤维肉瘤癌基因同源物 A（MAFA）是β细胞发育和成熟所必需的转录因子。NEUROG3 在内分泌祖细胞中表达，控制胰岛分化和再生。PDX1 对于胰腺外分泌和内分泌细胞（包括β细胞）的发育是必不可少的。PDX1 还与调节元件结合，增加胰岛素基因的转录。同样，MAFA 结合到胰岛素基因的增强子/启动子区域，响应葡萄糖驱动胰岛素表达。除了在β细胞发育和成熟中的这些自然作用外，PDX1、NEUROG3 和/或 MAFA 的异位表达已成功地用于在体外和体内将各种细胞类型重编程为产生胰岛素的细胞，如胰腺外分泌细胞、肝细胞和多能干细胞。在这里，我们回顾了 PDX1、NEUROG3 和 MAFA 的生物学特性，以及它们在β细胞再生方法中的应用和局限性。本综述的主要原始文献来源是使用 PubMed 搜索 1990 年至 2017 年期间发表的文章获得的。搜索词包括糖尿病、胰岛素、转分化、干细胞和再生医学。
