婆罗门相关基因1/婆罗门相关因子亚基在神经干/祖细胞及相关神经发育障碍中的作用

Role of brahma-related gene 1/brahma-associated factor subunits in neural stem/progenitor cells and related neural developmental disorders.

作者信息

Ke Nai-Yu, Zhao Tian-Yi, Wang Wan-Rong, Qian Yu-Tong, Liu Chao

机构信息

The First Clinical Medical College, Anhui Medical University, Hefei 230032, Anhui Province, China.

Institute of Stem cells and Tissue Engineering, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui Province, China.

出版信息

World J Stem Cells. 2023 Apr 26;15(4):235-247. doi: 10.4252/wjsc.v15.i4.235.

Abstract

Different fates of neural stem/progenitor cells (NSPCs) and their progeny are determined by the gene regulatory network, where a chromatin-remodeling complex affects synergy with other regulators. Here, we review recent research progress indicating that the BRG1/BRM-associated factor (BAF) complex plays an important role in NSPCs during neural development and neural developmental disorders. Several studies based on animal models have shown that mutations in the BAF complex may cause abnormal neural differentiation, which can also lead to various diseases in humans. We discussed BAF complex subunits and their main characteristics in NSPCs. With advances in studies of human pluripotent stem cells and the feasibility of driving their differentiation into NSPCs, we can now investigate the role of the BAF complex in regulating the balance between self-renewal and differentiation of NSPCs. Considering recent progress in these research areas, we suggest that three approaches should be used in investigations in the near future. Sequencing of whole human exome and genome-wide association studies suggest that mutations in the subunits of the BAF complex are related to neurodevelopmental disorders. More insight into the mechanism of BAF complex regulation in NSPCs during neural cell fate decisions and neurodevelopment may help in exploiting new methods for clinical applications.

摘要

神经干/祖细胞(NSPCs)及其后代的不同命运由基因调控网络决定,其中染色质重塑复合物会影响与其他调节因子的协同作用。在此,我们综述了近期的研究进展,这些进展表明BRG1/BRM相关因子(BAF)复合物在神经发育和神经发育障碍过程中的NSPCs中起着重要作用。多项基于动物模型的研究表明,BAF复合物中的突变可能导致神经分化异常,这也可能导致人类的各种疾病。我们讨论了NSPCs中BAF复合物的亚基及其主要特征。随着人类多能干细胞研究的进展以及将其诱导分化为NSPCs的可行性,我们现在能够研究BAF复合物在调节NSPCs自我更新与分化平衡中的作用。鉴于这些研究领域的最新进展,我们建议在不久的将来,研究中应采用三种方法。全人类外显子组测序和全基因组关联研究表明,BAF复合物亚基中的突变与神经发育障碍有关。更深入了解BAF复合物在神经细胞命运决定和神经发育过程中对NSPCs的调控机制,可能有助于开发新的临床应用方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0294/10173807/d0c3e3ed6a24/WJSC-15-235-g001.jpg

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