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. 2024 Mar 8;21:66. doi: 10.1186/s12974-024-03052-4

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 8 — Analysis of the HD microglia-specific transcriptome and the consequences of Tyrobp deletion. RNA was purified from freshly isolated striatal microglia and then sequenced. A Analysis of global levels of cell type-specific transcripts from sorted mouse microglia RNA-seq samples using geometric mean of the normalized counts of cell type marker genes of Drd1 (direct)-MSNs, Drd2 (indirect) -MSNs, astrocytes and microglia. B Volcano plot illustrating the DEGs identified in Q175 vs WT comparison. Only the genes with FDR < 0.1 are shown. C Heatmap of binomial p-values for Bioplanet pathways upregulated in human and mouse datasets. D Predicted upstream regulators of upregulated genes from Q175 microglia. E Intersection between genes with H3K27me3 marks from striatal microglia and upregulated genes from Q175 microglia. F Pathways associated with upregulated DEGs with a H3K27me3 mark. Color denotes database (Brown: Bioplanet; Green: KEGG pathways; Blue: Wikpathways). G Volcano plot illustrating the DEGs identified in Q175;Tyrobp^(−/−) vs Q175 comparison. Only the genes with FDR < 0.1 are shown. H Heatmap of binomial p-values for Bioplanet pathways decreased in Q175;Tyrobp^(−/−), and integration with increased pathways from specified human and mouse datasets. I KEGG pathways enriched for upregulated genes in the microglial cluster of HD human snRNA-seq (pink/gray), integrated with the pathways downregulated by Tyrobp deletion in Q175 mice (blue). J Western blot and densitometric analysis of phosphorylated and total Erk protein in striatal samples. n = 5–6 mice per group. Quantitative analysis is shown as mean ± SEM. Each point represents data from an individual mouse. Statistical analysis was performed using Two-Way ANOVA. *p < 0.05