State Key Laboratory of Cellular Stress Biology The First Affiliated Hospital of Xiamen University School of Life Sciences Xiamen University Xiamen 361102 China.
The Department of Neuroscience School of Medicine Xiamen University Xiamen 361102 China.
Adv Sci (Weinh). 2021 Mar 22;8(10):2003164. doi: 10.1002/advs.202003164. eCollection 2021 May.
Forming tight interaction with both Purkinje and granule cells (GCs), Bergmann glia (BG) are essential for cerebellar morphogenesis and neuronal homeostasis. However, how BG act in this process is unclear without comprehensive transcriptome landscape of BG. Here, high temporal-resolution investigation of transcriptomes with FACS-sorted BG revealed the dynamic expression of genes within given functions and pathways enabled BG to assist neural migration and construct neuron-glia network. It is found that the peak time of GCs migration (P7-10) strikingly coincides with the downregulation of extracellular matrix (ECM) related genes, and the disruption of which by Setdb1 ablation at P7-10 in BG leads to significant migration defect of GCs emphasizing the criticality of Nfix-Setdb1 mediated H3K9me3 repressive complex for the precise regulation of GCs migration in vivo. Thus, BG's transcriptomic landscapes offer an insight into the mechanism by which BG are in depth integrated in cerebellar neural network.
与浦肯野细胞和颗粒细胞（GCs）紧密相互作用，Bergmann 胶质细胞（BG）对于小脑形态发生和神经元稳态至关重要。然而，如果没有 BG 的全面转录组景观，就不清楚 BG 如何在这个过程中发挥作用。在这里，通过 FACS 分选的 BG 进行高时间分辨率的转录组研究揭示了特定功能和途径内基因的动态表达，使 BG 能够协助神经迁移并构建神经元-胶质细胞网络。研究发现，GCs 迁移的高峰期（P7-10）与细胞外基质（ECM）相关基因的下调明显吻合，而在 P7-10 时通过 Setdb1 消融破坏 BG 中的 ECM 相关基因会导致 GCs 迁移的显著缺陷，这强调了 Nfix-Setdb1 介导的 H3K9me3 抑制复合物对于体内 GCs 迁移的精确调控的关键性。因此，BG 的转录组景观提供了一个深入了解 BG 如何深入整合到小脑神经网络中的机制的视角。
