Fig. 5

Transcriptome analysis of cortical astrocytes after MACS via ACSA2 of MBP29-hα-syn mice. A Mosaic plot of altered astrocytic functions in the cortex of MBP29-hα-syn mice based on existing dataset [16]. Reactivity profile of cortical astrocytes show less pronounced upregulation of reactivity-associated genes compared to striatal astrocytes. Primary processes affected refer to metabolic and ECM organization, as well as unclassified processes. B Volcano plot of DEGs analyzed comparing MBP29-hα-syn mice with non-transgenic litter mates. Thresholds were set to log2foldchange > 2.0 and adj. p value < 0.05. Y-axis: negative decade logarithm of adj. p value. X-axis: log2foldchange of gene expression levels. In turquoise: significantly downregulated genes, in grey: genes without statistical significance, in red: significantly upregulated genes. Transcripts with most significant adj. p-values and log2foldchange were visualized using official gene symbols by HGNC. C, D Heatmap of the 20 most highly up- and downregulated genes according to adjusted p value. Gene expression was scaled by rows to visualize differences in gene expression between and within the genotypes using log2foldchange of gene expression. Cortical astrocytes display significant upregulation of transcripts associated with oligodendrocyte development and myelination (ERMN, MAG, MYRF, OPALIN), ion and neurotransmitter homeostasis, and neuroprotection (SLC6A7, TLL2, SLCA24A2, SIS). E, F Functional gene set enrichment analysis of DEGs (FDR > 0.05). Pathways are ordered by normalized enrichment score (NES). Nomenclature of pathways is modified from official hallmark and biological processes pathways. E Transcripts enriched in protein secretion are upregulated in cortical astrocytes, whereas a significant downregulation of transcripts enriched in pro-inflammatory processes (IL-6/STAT3, complement, IFNγ, IFNα) was observed. F Upregulated transcripts demonstrate enrichment in receptor-mediated endocytosis and amyloid-β metabolism. Enrichment of downregulated transcripts mostly in immune system associated processes (complement, dendritic cell activation) confirms pattern already observed in hallmark analysis