Department of Pharmacy, Xiangya Hospital, Central South University, No.87 Xiangya Road, Changsha, 410008, People's Republic of China.
Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.
Mol Cancer. 2024 Aug 1;23(1):153. doi: 10.1186/s12943-024-02066-z.
The hallmarks of stem cells, such as proliferation, self-renewal, development, differentiation, and regeneration, are critical to maintain stem cell identity which is sustained by genetic and epigenetic factors. Super-enhancers (SEs), which consist of clusters of active enhancers, play a central role in maintaining stemness hallmarks by specifically transcriptional model. The SE-navigated transcriptional complex, including SEs, non-coding RNAs, master transcriptional factors, Mediators and other co-activators, forms phase-separated condensates, which offers a toggle for directing diverse stem cell fate. With the burgeoning technologies of multiple-omics applied to examine different aspects of SE, we firstly raise the concept of "super-enhancer omics", inextricably linking to Pan-omics. In the review, we discuss the spatiotemporal organization and concepts of SEs, and describe links between SE-navigated transcriptional complex and stem cell features, such as stem cell identity, self-renewal, pluripotency, differentiation and development. We also elucidate the mechanism of stemness and oncogenic SEs modulating cancer stem cells via genomic and epigenetic alterations hijack in cancer stem cell. Additionally, we discuss the potential of targeting components of the SE complex using small molecule compounds, genome editing, and antisense oligonucleotides to treat SE-associated organ dysfunction and diseases, including cancer. This review also provides insights into the future of stem cell research through the paradigm of SEs.
干细胞的特征，如增殖、自我更新、发育、分化和再生，对于维持干细胞的身份至关重要，这种身份是由遗传和表观遗传因素维持的。超级增强子（SEs）由活跃的增强子簇组成，通过特定的转录模型在维持干细胞特征方面发挥核心作用。SE 导航转录复合物，包括 SEs、非编码 RNA、主转录因子、中介体和其他共激活因子，形成相分离的凝聚物，为指导不同的干细胞命运提供了一个切换开关。随着多组学技术的蓬勃发展，用于检查 SE 的不同方面，我们首先提出了“超级增强子组学”的概念，与泛组学密不可分。在综述中，我们讨论了 SE 的时空组织和概念，并描述了 SE 导航转录复合物与干细胞特征之间的联系，如干细胞身份、自我更新、多能性、分化和发育。我们还阐明了通过基因组和表观遗传改变劫持癌症干细胞中的干细胞特性和致癌 SE 调节癌症干细胞的机制。此外，我们还讨论了使用小分子化合物、基因组编辑和反义寡核苷酸靶向 SE 复合物成分来治疗与 SE 相关的器官功能障碍和疾病（包括癌症）的潜力。通过 SE 的范例，本综述还为干细胞研究的未来提供了一些见解。
