胰腺发育过程中细胞命运的表观遗传调控

Trends in developmental biology Pub Date : 2023-01-01
Shilpak Bele, Anthony S Wokasch, Maureen Gannon
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引用次数: 0

摘要

DNA 及其相关蛋白的表观遗传修饰会影响整个胚胎发育过程中的细胞可塑性和细胞命运限制。脊椎动物胰腺发育的特点是,在后前肠内胚层的一个确定区域,一组转录调控因子最初是重叠表达的,它们共同促进胰腺祖细胞的分化和增殖。随着发育的进行,这些转录因子会分离成不同的胰腺系,其中一些转录因子会在整个成年期维持在终末分化的胰腺细胞类型的特定亚群中。在这里,我们描述了胰腺发育过程中的渐进阶段和细胞命运限制,以及驱动调控胰腺发育的转录因子动态表达模式的相关已知表观遗传调控事件。此外,我们还强调了表观遗传标记的变化如何影响对胰腺疾病(如糖尿病)的易感性、成年胰腺细胞的可塑性以及产生替代胰岛素分泌β细胞治疗糖尿病的能力。
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Epigenetic modulation of cell fate during pancreas development.

Epigenetic modifications to DNA and its associated proteins affect cell plasticity and cell fate restrictions throughout embryonic development. Development of the vertebrate pancreas is characterized by initial is an over-lapping expression of a set of transcriptional regulators in a defined region of the posterior foregut endoderm that collectively promote pancreas progenitor specification and proliferation. As development progresses, these transcription factors segregate into distinct pancreatic lineages, with some being maintained in specific subsets of terminally differentiated pancreas cell types throughout adulthood. Here we describe the progressive stages and cell fate restrictions that occur during pancreas development and the relevant known epigenetic regulatory events that drive the dynamic expression patterns of transcription factors that regulate pancreas development. In addition, we highlight how changes in epigenetic marks can affect susceptibility to pancreas diseases (such as diabetes), adult pancreas cell plasticity, and the ability to derive replacement insulin-producing β cells for the treatment of diabetes.

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