BCL7A-containing SWI/SNF/BAF complexes modulate mitochondrial bioenergetics during neural progenitor differentiation.

Mammalian SWI/SNF/BAF chromatin remodeling complexes influence cell lineage determination. While the contribution of mammalian SWI/SNF/BAF complexes in neural progenitor cell (NPC) proliferation and differentiation has been reported, little is known about the transcriptional profiles that determine neurogenesis or gliogenesis. Here we report that BCL7A is a modulator of the SWI/SNF/BAF complex and stimulates the genome-wide occupancy of the ATPase BRG1. We demonstrate that BCL7A is dispensable for SWI/SNF/BAF complex integrity, whereas it is essential to regulate Notch/Wnt pathway and mitochondrial bioenergetics in differentiating NPCs. Together, our findings uncover the unique mechanistic contribution of BCL7A-containing SWI/SNF/BAF complex in mitochondria-driven NPC commitment, thereby providing a better understanding of the cell-intrinsic transcriptional processes that connect metabolism, neuronal morphogenesis and cognitive flexibility. Overall design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for SMARCA4/BRG1 in mouse and iPSC-derived BCL7A KO NPCs

哺乳动物SWI/SNF/BAF染色质重塑复合物（chromatin remodeling complexes）可调控细胞谱系决定。尽管已有研究报道该复合物在神经祖细胞（neural progenitor cell, NPC）增殖与分化中的功能，但目前对于决定神经发生或胶质发生的转录调控谱仍知之甚少。本研究发现，BCL7A是SWI/SNF/BAF复合物的调控因子，能够促进ATP酶BRG1在全基因组范围内的结合占据。研究证实，BCL7A对于维持SWI/SNF/BAF复合物的完整性并非必需，却是分化中NPC调控Notch/Wnt通路与线粒体生物能学的关键因子。综上，本研究揭示了含BCL7A的SWI/SNF/BAF复合物在线粒体驱动的NPC细胞定型中的独特机制，从而增进了人们对连接代谢、神经元形态发生与认知灵活性的细胞内在转录过程的理解。实验设计：对小鼠及诱导多能干细胞（induced pluripotent stem cell, iPSC）来源的BCL7A敲除（knockout, KO）神经祖细胞中的SMARCA4/BRG1进行染色质免疫共沉淀测序（Chromatin immunoprecipitation DNA-sequencing, ChIP-seq）