Department of Biological Sciences, Sunandan Divatia School of Science, SVKM's NMIMS (deemed to-be) University, Mumbai 400 056, India.
Symbiosis Centre for Stem Cell Research (SCSCR), Symbiosis International University, Lavale, Pune 412 115, India.
Mech Dev. 2020 Dec;164:103647. doi: 10.1016/j.mod.2020.103647. Epub 2020 Sep 28.
The dual nature of pancreatic tissue permits both endocrine and exocrine functions. Enzymatic secretions by the exocrine pancreas help digestive processes while the pancreatic hormones regulate glucose homeostasis and energy metabolism. Pancreas organogenesis is defined by a conserved array of signaling pathways that act on common gut progenitors to bring about the generation of diverse cell types. Multiple cellular processes characterize development of the mature organ. These processes are mediated by signaling pathways that regulate lineage-specific transcription factors and chromatin modifications guiding long-term gene expression programs. The chromatin landscape is altered chiefly by DNA or histone modifications, chromatin remodelers, and non-coding RNAs. Amongst histone modifiers, several studies have identified Polycomb group (PcG) proteins as crucial determinants mediating transcriptional repression of genes involved in developmental processes. Although PcG-mediated chromatin modifications define cellular transitions and influence cell identity of multipotent progenitors, much remains to be understood regarding coordination between extracellular signals and their impact on Polycomb functions during the pancreas lineage progression. In this review, we discuss interactions between sequence-specific DNA binding proteins and chromatin regulators underlying pancreas development and insulin producing β-cells, with particular focus on Polycomb group proteins. Understanding such basic molecular mechanisms would improve current strategies for stem cell-based differentiation while also help elucidate the pathogenesis of several pancreas-related maladies, including diabetes and pancreatic cancer.
胰腺组织具有双重性质，既能发挥内分泌功能，也能发挥外分泌功能。外分泌胰腺的酶分泌有助于消化过程，而胰腺激素则调节葡萄糖稳态和能量代谢。胰腺发生是由一系列保守的信号通路定义的，这些信号通路作用于共同的肠道祖细胞，产生不同的细胞类型。多种细胞过程特征是成熟器官的发育。这些过程由信号通路介导，这些信号通路调节谱系特异性转录因子和染色质修饰，指导长期的基因表达程序。染色质景观主要通过 DNA 或组蛋白修饰、染色质重塑因子和非编码 RNA 来改变。在组蛋白修饰物中，有几项研究已经确定多梳组（PcG）蛋白作为关键决定因素，介导参与发育过程的基因的转录抑制。尽管 PcG 介导的染色质修饰定义了细胞转变，并影响多能祖细胞的细胞身份，但关于细胞外信号的协调及其对胰腺谱系进展过程中多梳功能的影响，仍有许多需要了解。在这篇综述中，我们讨论了在胰腺发育和胰岛素产生β细胞中，序列特异性 DNA 结合蛋白和染色质调节剂之间的相互作用，特别关注多梳组蛋白。了解这些基本的分子机制将改善基于干细胞的分化的现有策略，同时也有助于阐明包括糖尿病和胰腺癌在内的几种与胰腺相关疾病的发病机制。
