Fig. 5: Properties and mechanisms of Crym⁺ and Crym⁻ astrocytes.

a, UMAP of striatal astrocytes segregated by Crym expression. b, Violin plot of 10 astrocyte markers in Crym⁺ and Crym⁻ astrocytes. c, Volcano plot of differentially expressed genes between Crym⁺ and Crym⁻ astrocytes. d, The top 20 most (FDR < 0.05) enriched genes and the 20 most depleted 20 genes in Crym⁺ astrocytes (scale bar, log₂FC). Top 40 shared genes (of 2,520) in grey (scale bar, log₂FC). Ingenuity pathway analysis (IPA) based top ten shared pathways for Crym⁺ and Crym⁻ astrocytes and the top ten unique pathways for Crym⁺ astrocytes. NGF, nerve growth factor. IGF, insulin like growth factor. IGFBP, insulin like growth factor binding protein. Nt, neurotransmitter. LPS, lipopolysaccharide. e, Interaction map of 78 µ-crystallin interacting proteins. Node sizes represent enrichment compared to GFP. Edge colours represent the SAINT protein–protein interaction probability score. All proteins had a SAINT Bonferroni-corrected false discovery rate (BFDR) less than 0.05. f, Clustergram of common and unique proteins (78 proteins) detected in Crym-BioID2 relative to astrocyte-specific subcompartments. Proteins represent those that were significant after normalization (log₂FC > 1 and FDR < 0.05 versus GFP controls). g, Schematic of the PLA. h, Images of PLA puncta for µ-crystallin and MAP2 in tdTomato (tdT)-positive astrocytes. Graph: puncta per tdT⁺ astrocyte in control experiments (ctrl), central (C) and dorsolateral (DL) striatum. Scale bars, 15 μm. i, As in h, but for and µ-crystallin and USP9X (n  =  18 and 21 tdTomato⁺ astrocytes from 4 mice per group, one-way ANOVA followed by Tukey’s post-hoc test). Scale bars, 15 μm. j, Abundance of µ-crystallin interactors in different astrocyte subcompartments from f. The bottom heat map shows log₂FC of the μ-crystallin interactors from human OCD⁵ and HD⁶ post-mortem RNA-seq. Average data shown as mean ± s.e.m. and all statistics reported in Supplementary Table 5.

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