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. 2024 Feb 28;627(8003):358–366. doi: 10.1038/s41586-024-07138-0

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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/.

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Fig. 1 — a, Top 20 striatal-astrocyte-enriched genes from RNA-seq¹⁵ of 13 brain areas: OB, olfactory bulb; MCX, motor cortex; SCX, somatosensory cortex; VCX, visual cortex; HIP, hippocampus; STR, striatum; TH, thalamus; HY, hypothalamus; CB, cerebellum; MB, midbrain; HB, hindbrain; DSC, dorsal spinal cord; VSC, ventral spinal cord. The fragments per kilobase per million mapped fragments (FPKM) z-score shows the 20 striatal-astrocyte-enriched genes as compared with other areas and their enrichment (log₂ immunoprecipitated (IP)/input). The orphan gene 9330182L06RiK has been abbreviated as 93...RiK in a. The other heat maps show the genes plotted from bulk RNA-seq data from human OCD⁵ and HD⁶ and in astrocytes from individuals with HD⁷ relative to control individuals. b, scRNA-seq of two-month-old striatum optimized for cellular diversity²³, as seen in cell-class percentages. Uniform manifold approximation and projection (UMAP) of 39,156 cells from the striatum shows cell classes, including astrocytes. Violin plots show astrocyte enrichment of Gja1 and Crym (n = 4 mice). OLG, oligodendrocytes; AST, astrocytes; MG, microglia; NSCs, neural stem cells; ECs, endothelial cells; NEU, neurons; OPCs, oligodendrocyte precursor cells; MCs, mural cells; EP, ependymal cells. c, Crym was expressed in around 50% of astrocytes; astrocytic markers were found in more. d, Crym mRNA expression along with S100β IHC; inset higher magnification (representative of n = 16 sections from 4 mice). Scale bars, 500 μm (main); 20 μm (inset). CC, corpus callosum. AC, anterior commissure. e, Images of µ-crystallin (magenta) and astrocytic S100β (green) IHC. µ-crystallin shows a dorsoventral and lateromedial spatial gradient (CTX, cortex; SVZ, subventricular zone; DL, dorsolateral striatum; DM, dorsomedial striatum; CL, centrolateral striatum; CM, centromedial striatum). Scale bar, 200 μm. f, Magnified images of µ-crystallin (magenta) and SOX9 (green), and μ-crystallin and S100β (green) IHC in the centromedial striatum (CM). μ-crystallin and NeuN IHC in the SVZ are also shown. Scale bars, 40 μm. g,h, Percentage of astrocytes (g; S100β⁺ and SOX9⁺) and neurons (h; NeuN⁺) expressing µ-crystallin (n = 4, 8 and 7 mice for SOX9, S100β and NeuN, respectively). The white arrows in panels d and f point to instances of co-localization in the images. Average data shown as mean ± s.e.m. and all statistics reported in Supplementary Table 5.

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