研究动态
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干细胞中的超级增强子组学。

Super-enhancer omics in stem cell.

发表日期:2024 Aug 01
作者: Hongying Ma, Jian Qu, Zicheng Pang, Jian Luo, Min Yan, Weixin Xu, Haihui Zhuang, Linxin Liu, Qiang Qu
来源: Molecular Cancer

摘要:

干细胞的特征,例如增殖、自我更新、发育、分化和再生,对于维持由遗传和表观遗传因素维持的干细胞特性至关重要。超级增强子(SE)由活性增强子簇组成,通过特定的转录模型在维持干性特征方面发挥着核心作用。 SE 导航的转录复合物,包括 SE、非编码 RNA、主转录因子、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开关。随着多组学技术应用于研究SE不同方面的新兴技术,我们首先提出了“超级增强组学”的概念,与泛组学有着千丝万缕的联系。在这篇综述中,我们讨论了 SE 的时空组织和概念,并描述了 SE 导航的转录复合体与干细胞特征之间的联系,例如干细胞身份、自我更新、多能性、分化和发育。我们还阐明了干性和致癌 SE 通过基因组和表观遗传改变劫持癌症干细胞来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 SE 相关器官功能障碍和疾病(包括癌症)的潜力。这篇综述还通过 SE 范式提供了对干细胞研究未来的见解。© 2024。作者。
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.© 2024. The Author(s).