Epigenetic Control of Smooth Muscle Cell Identity and Lineage Memory.
Epigenetic Control of Smooth Muscle Cell Identity and Lineage Memory.
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DOI：
10.1161/atvbaha.115.305044
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Owens GK
中科院分区：
文献类型：
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作者：
Gomez D;Swiatlowska P;Owens GK
血管平滑肌细胞（SMC），像所有的细胞一样，在发育过程中获得细胞特异性表观遗传特征，包括获得独特的组蛋白和DNA修饰库。这些变化被假定为在分化的SMC中表达的基因库上诱导开放染色质状态（称为常染色质），包括SMC选择性标记基因如Acta2和Myh11，以及大多数细胞类型表达的管家基因。相反，在分化的SMC中沉默的基因获得与闭合染色质状态（即异染色质）和转录沉默相关的修饰。在此，我们审查机制，规范SMC的分化状态的表观遗传控制。此外，我们确定了该领域的一些主要限制和未来的挑战，包括开发创新的新工具和方法，用于进行单细胞表观遗传测定和表观基因组的基因座选择性编辑，这将允许直接研究发育，损伤修复和疾病（包括主要心血管疾病，如动脉粥样硬化，高血压，和与糖尿病相关的微血管疾病。
Vascular smooth muscle cells (SMC), like all cells, acquire a cell-specific epigenetic signature during development that includes acquisition of a unique repertoire of histone and DNA modifications. These changes are postulated to induce an open chromatin state (referred to as euchromatin) on the repertoire of genes that are expressed in differentiated SMC including SMC-selective marker genes like Acta2 and Myh11, as well as housekeeping genes expressed by most cell types. In contrast, genes that are silenced in differentiated SMC acquire modifications associated with a closed chromatin state (i.e. heterochromatin) and transcriptional silencing. Herein we review mechanisms that regulate epigenetic control of the differentiated state of SMC. In addition, we identify some of the major limitations in the field and future challenges including development of innovative new tools and approaches for performing single-cell epigenetic assays and locus-selective editing of the epigenome that will allow direct studies of the functional role of specific epigenetic controls during development, injury-repair, and disease including major cardiovascular diseases such as atherosclerosis, hypertension, and microvascular disease associated with diabetes.