染色质结构的表观遗传重塑：在间充质干细胞和肉瘤中探索肿瘤分化疗法。
Epigenetic remodeling of chromatin architecture: exploring tumor differentiation therapies in mesenchymal stem cells and sarcomas.
机构信息
Integrated Program, Graduate School of Arts and Sciences, New York, USA.
出版信息
Curr Stem Cell Res Ther. 2010 Mar;5(1):63-73. doi: 10.2174/157488810790442859.
Abstract
Sarcomas are the mesenchymal-derived malignant tumors of connective tissues (e.g., fat, bone, and cartilage) presumed to arise from aberrant development or differentiation of mesenchymal stem cells (MSCs). Appropriate control of stem cell maintenance versus differentiation allows for normal connective tissue development. Current theories suggest that loss of this control--through accumulation of genetic lesions in MSCs at various points in the differentiation process--leads to development of sarcomas, including undifferentiated, high grade sarcoma tumors. The initiation of stem cell differentiation is highly associated with alteration of gene expression, which depends on chromatin remodeling. Epigenetic chromatin modifying agents have been shown to induce cancer cell differentiation and are currently being used clinically to treat cancer. This review will focus on the importance of epigenetic chromatin remodeling in the context of mesenchymal stem cells, sarcoma tumorigenesis and differentiation therapy.
摘要
肉瘤是源自间充质细胞（例如脂肪、骨和软骨）的间叶源性恶性肿瘤，被认为是起源于间充质干细胞（MSCs）的异常发育或分化。适当控制干细胞的维持与分化可以促进正常的结缔组织发育。目前的理论表明，通过在分化过程中的不同点在 MSCs 中积累遗传损伤，这种控制的丧失会导致肉瘤的发展，包括未分化的高级别肉瘤肿瘤。干细胞分化的启动与基因表达的改变密切相关，这取决于染色质重塑。已经证明表观遗传染色质修饰剂可诱导癌细胞分化，并正在临床上用于治疗癌症。这篇综述将重点介绍表观遗传染色质重塑在间充质干细胞、肉瘤发生和分化治疗中的重要性。
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