Oral and Pharyngeal Cancer Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD, United States.
Curr Opin Cell Biol. 2013 Apr;25(2):162-9. doi: 10.1016/j.ceb.2013.01.009. Epub 2013 Feb 19.
The squamous epithelium covering the skin and oral mucosa relies on epithelial stem cells for tissue renewal. Dynamic changes in DNA methylation, histone methylation and acetylation, and higher order chromatin structure are required to preserve their self-renewal capacity while orchestrating the timely execution of cell differentiation programs. This complex network of epigenetic modifications shapes the epithelial stem cell identity and fate. Pathological alterations can be perceived by aberrant chromatin sensors, such as the INK4/ARF locus, which initiate tumor suppressive cell senescence programs, and can often result in epithelial stem cell exhaustion. Unveiling the mechanisms controlling the epigenome in epithelial stem cells may help protect against the loss of their tissue regenerative capacity, thereby preventing premature aging without increasing cancer risk.
覆盖皮肤和口腔黏膜的鳞状上皮依赖于上皮干细胞来进行组织更新。为了在协调细胞分化程序的同时维持其自我更新能力，需要动态地改变 DNA 甲基化、组蛋白甲基化和乙酰化以及更高阶的染色质结构。这种复杂的表观遗传修饰网络塑造了上皮干细胞的特性和命运。异常的染色质传感器，如 INK4/ARF 基因座，可以感知到病理性改变，从而启动肿瘤抑制细胞衰老程序，并且常常导致上皮干细胞衰竭。揭示控制上皮干细胞中表观基因组的机制可能有助于防止其组织再生能力的丧失，从而预防过早衰老，而不会增加癌症风险。
