Temporarily Epigenetic Repression in Bergmann Glia Regulates the Migration of Granule Cells

Abstract

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.

A method for differential expression analysis and pseudo-temporal locating and ordering of genes in single-cell transcriptomic data

“…7e). It has been reported that the three genes regulate the function of Purkinje cells [31][32][33] . Therefore, the specific expression patterns of these three genes indicate that this narrow region (cluster 12) is composed of Purkinje cells, which is consistent with the existing reports that the mature cerebellar cortex is composed of three layers: inner granular layer, Purkinje cell layer and molecular layer 34 .…”