Departments of Pediatrics and Cellular & Molecular Medicine, Pediatric Diabetes Research Center, University of California, San Diego, La Jolla, California 92093, USA.
Genes Dev. 2019 Nov 1;33(21-22):1475-1490. doi: 10.1101/gad.331397.119.
A comprehensive understanding of mechanisms that underlie the development and function of human cells requires human cell models. For the pancreatic lineage, protocols have been developed to differentiate human pluripotent stem cells (hPSCs) into pancreatic endocrine and exocrine cells through intermediates resembling in vivo development. In recent years, this differentiation system has been employed to decipher mechanisms of pancreatic development, congenital defects of the pancreas, as well as genetic forms of diabetes and exocrine diseases. In this review, we summarize recent insights gained from studies of pancreatic hPSC models. We discuss how genome-scale analyses of the differentiation system have helped elucidate roles of chromatin state, transcription factors, and noncoding RNAs in pancreatic development and how the analysis of cells with disease-relevant mutations has provided insight into the molecular underpinnings of genetically determined diseases of the pancreas.
要全面了解人类细胞的发育和功能的机制，就需要用到人类细胞模型。对于胰腺谱系来说，已经开发出了通过类似于体内发育的中间产物将人类多能干细胞(hPSC)分化为胰腺内分泌和外分泌细胞的方案。近年来，这种分化系统被用于解析胰腺发育、胰腺先天缺陷以及遗传形式的糖尿病和外分泌疾病的机制。在这篇综述中，我们总结了从胰腺 hPSC 模型研究中获得的最新见解。我们讨论了分化系统的全基因组分析如何帮助阐明染色质状态、转录因子和非编码 RNA 在胰腺发育中的作用，以及对具有相关疾病突变的细胞的分析如何深入了解胰腺遗传疾病的分子基础。
