| Functional performance of cerebellum relies on a fully integrated network of neurons and glia cells.Forming tight interaction with both Purkinje cells(PCs)and granule cells(GCs),Bergmann glia(BG)are essential for cerebellar morphogenesis and neuronal homeostasis.However,the mechanism of which is unclear for the limited transcriptome of BG.Here,we screened two mouse models(NesGFP and Mash1 iTom mices)to specifically label infancy and adult BGs and obtained a high temporalresolution investigation of transcriptomes with FACS-sorted BG within 2 months.According to these profiles,we found many new BG marker genes and found that BGs were in the developmental stage before P16(postnatal day 16),the expression of genes were highly dynamic,but after P30,they were in the mature stage,and the expression profile was stable.To our surprise,the genes that changed in each developmental stages are basically different but with similar functions which related to BG interaction with other cells.Then we focus on a transient time window at postnatal day7-10(P7-10),the "rush hour" of granule cell(GC)-migration and cerebellum morphogenesis,strikingly coinciding with the downregulation of extracellular matrix(ECM)related genes by prevailing transcriptional repression.Disrupting of ECM genes by Setdbl ablation at P7-10 in BG led to the significant migration defect of GCs.Emphasizing the criticality of NFIX-Setdb1 mediated H3K9me3 repressive complex for the precise regulation of GC 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.Our study reveals for the first time a mechanism by which Setdb1-dependent epigenetic regulation promotes accurate development of BG,and provide a transcriptional summarization of BG development at distinct stages that will serve as a valuable resource for future investigations of BG development,neurobiology,and disease. |
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