Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Curr Opin Endocrinol Diabetes Obes. 2013 Feb;20(1):1-7. doi: 10.1097/MED.0b013e32835bc380.
We highlight some of the major recent advances that have been made towards understanding the mechanisms that control endocrine differentiation and cell identity in the pancreas and intestine.
Notch signaling plays a complex role in the fate choice between endocrine, duct, and acinar lineages in the developing pancreas. New approaches to dissecting the role of mesenchymal cells in the developing endocrine pancreas reveal inhibitory signals from the endothelium. Epigenetic mechanisms represent another layer of control over pancreatic development and β cell identity. Further details on the transcriptional control of enteroendocrine cell development have emerged and revealed a surprising role for FoxO1 in restraining insulin expression in the gut. Incremental progress is being made in the field of directed differentiation of embryonic stem cells to pancreatic β cells and the first reported differentiation of human embryonic stem cells into intestinal organoids containing enteroendocrine cells represents a major breakthrough.
Greater knowledge of the fundamental processes controlling endocrine development in the pancreas and intestine has the potential to advance the field of regenerative medicine by providing a pathway to successfully create cell types of clinical interest.
目的综述:我们强调了一些近期在理解胰腺和肠道内分泌分化和细胞特性的调控机制方面取得的重大进展。
新发现:Notch 信号在胰腺发育过程中内分泌、导管和腺泡谱系之间的命运选择中发挥着复杂的作用。解析发育中内分泌胰腺中间质细胞作用的新方法揭示了来自内皮细胞的抑制信号。表观遗传机制是对胰腺发育和β细胞特性的另一种控制方式。肠内分泌细胞发育的转录控制的更多细节已经出现,并揭示了 FoxO1 在抑制肠道中胰岛素表达方面的惊人作用。在胚胎干细胞向胰腺β细胞的定向分化领域取得了渐进式的进展,首例报道的人类胚胎干细胞分化为含有肠内分泌细胞的肠类器官是一个重大突破。
总结:对胰腺和肠道内分泌发育的基本过程的更深入了解,有可能通过提供一条成功创建具有临床意义的细胞类型的途径,推动再生医学领域的发展。