The loss of functional β cells leads to development of diabetes. Several studies have shown that β cells are specified through several stages of progenitors during pancreas development, each stage defined by the expression of specific transcription factors (TFs). Understanding signalling pathways that control the differentiation and specification processes during embryogenesis will facilitate efforts to obtain functional β cells in vitro. Our current knowledge of the mechanisms involved in pancreatic β cell development and survival under normal or diabetic conditions has come largely from animal studies. However, there are marked differences in islet structure and physiological properties between humans and animals, and not all phenotypes of human diabetes can be recapitulated in animal models. Therefore, human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced PSCs (hiPSCs) offer a great opportunity for increasing our understanding of the pathways regulating human pancreatic β‐cell development and survival. Furthermore, hPSCs provide a renewable source of functional pancreatic β cells for cell replacement therapy as well as disease modelling. Herein, we discuss the signalling pathways involved in the development of pancreatic β cells during embryogenesis. Additionally, we describe how these pathways are manipulated in vitro to differentiate hPSCs into functional β cells. Finally, we highlight the progress that has been made for the applications of those cells in treating and modelling diabetes.

中文翻译：

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控制干细胞衍生的胰腺 β 细胞发育的途径：胚胎发生的经验教训

功能性β细胞的丧失导致糖尿病的发展。几项研究表明，β 细胞在胰腺发育过程中通过祖细胞的几个阶段指定，每个阶段由特定转录因子 (TF) 的表达定义。了解在胚胎发生过程中控制分化和特化过程的信号通路将有助于在体外获得功能性 β 细胞的努力。我们目前对正常或糖尿病条件下胰腺 β 细胞发育和存活所涉及的机制的了解主要来自动物研究。然而，人和动物之间的胰岛结构和生理特性存在显着差异，并且并非所有人类糖尿病的表型都可以在动物模型中重现。因此，人类多能干细胞（hPSCs），包括人类胚胎干细胞 (hESCs) 和人类诱导的 PSCs (hiPSCs) 为增加我们对调节人类胰腺 β 细胞发育和存活的途径的理解提供了一个很好的机会。此外，hPSC 为细胞替代疗法和疾病建模提供了功能性胰腺 β 细胞的可再生来源。在此，我们讨论了胚胎发生过程中胰腺 β 细胞发育所涉及的信号通路。此外，我们描述了如何在体外操纵这些途径以将 hPSC 分化为功能性 β 细胞。最后，我们强调了这些细胞在糖尿病治疗和建模方面的应用所取得的进展。