Project description:Numerous literatures report similar time points are important in astrocyte development and transition from neurogenesis to gliogenesis. However, these developmental time points have not been studied in the perspective of chromatin state and the resulting transcriptional changes. In addition, the characteristics of astrocyte in different developmental time point is still unclear. Therefore, we examined the transcriptome and open chromatin regions of astrocytes during its development.
Project description:Chromosomes and genes are non-randomly arranged within the mammalian cell nucleus. Clustering of genes is of great significance in transcriptional regulation. However, the relevance of gene clustering in their expression during differentiation of neural precursor cells (NPCs) into astrocytes remains unclear. We performed a genome-wide enhanced circular chromosomal conformation capture (e4C) to screen genes associated with an astrocyte-specific gene, glial fibrillary acidic protein (Gfap), during astrocyte differentiation. We identified 13 genes that were specifically associated with Gfap and expressed in NPC-derived astrocytes. These results provide evidence for functional significance of gene clustering in transcriptional regulation during NPCs differentiation. comparison of NPCs vs LIF+ vs LIF- cells.
Project description:Lineage development is a step-wise process, governed by stage-specific regulatory factors and associated markers. Astrocytes are one of the principle cell types in the CNS and the stages associated with their development remain very poorly defined. To identify these stages we performed gene expression profiling on astrocyte precursor populations in the spinal cord, identifying distinct patterns of gene induction during their development. Validation studies identified a new cohort of astrocyte-associated genes during development and demonstrated their expression in reactive astrocytes in human white matter injury (WMI).
Project description:To gain futher insight into how astrocyte-derived PD1 regulates astrocyte morphogenesis and myelination, RNA-seq was used to analyze the genome-wide changes resulting from isolated astrocyte of P5 astrocyte-PD1 conditional knock out mice and littermate wild-type. Approximately six thousand transcripts showed differential expression between the Pd1fl/fl and Pd1cKO-Aldh1l1 mice brain astrocyte, with a fold change ≥3 and p value <0.05.Geneontology analysis of the downregulated genes were enriched in terms related to negative regulation of signal transduction, positive regulation of actin nucleation and upregulated genes were enriched in terms related to inflammatory response, positive regulation of ERK1 and ERK2 cascade and cell surface receptor signaling pathway. These results reflected astrocyte-PD1 plays roles in astrocyte development.