Huntington Disease (HD) is an inherited movement disorder caused by expanded CAG repeats in the Huntingtin gene. We have used single nucleus RNASeq (snRNASeq) to uncover cellular phenotypes that change in the disease, investigating single cell gene expression in cingulate cortex of patients with HD and comparing the gene expression to that of patients with no neurological disease. In this study, we focused on astrocytes, although we found significant gene expression differences in neurons, oligodendrocytes, and microglia as well. In particular, the gene expression profiles of astrocytes in HD showed multiple signatures, varying in phenotype from cells that had markedly upregulated metallothionein and heat shock genes, but had not completely lost the expression of genes associated with normal protoplasmic astrocytes, to astrocytes that had substantially upregulated glial fibrillary acidic protein (GFAP) and had lost expression of many normal protoplasmic astrocyte genes as well as metallothionein genes. When compared to astrocytes in control samples, astrocyte signatures in HD also showed downregulated expression of a number of genes, including several associated with protoplasmic astrocyte function and lipid synthesis. Thus, HD astrocytes appeared in variable transcriptional phenotypes, and could be divided into several different "states", defined by patterns of gene expression. Ultimately, this study begins to fill the knowledge gap of single cell gene expression in HD and provide a more detailed understanding of the variation in changes in gene expression during astrocyte "reactions" to the disease.

中文翻译：

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单核RNA-seq可鉴定亨廷顿病星形胶质细胞的状态。

亨廷顿病（HD）是由亨廷顿基因中CAG重复序列扩增引起的遗传性运动障碍。我们已经使用单核RNASeq（snRNASeq）揭示了疾病变化的细胞表型，研究了HD患者扣带回皮层中的单细胞基因表达，并将该基因表达与无神经系统疾病的患者进行了比较。在这项研究中，我们专注于星形胶质细胞，尽管我们发现神经元，少突胶质细胞和小胶质细胞也存在明显的基因表达差异。特别是，HD中星形胶质细胞的基因表达谱显示出多个特征，其表型与那些明显上调金属硫蛋白和热休克基因但尚未完全丧失与正常原生质体星形胶质细胞相关的基因表达的细胞不同，星形胶质细胞的表达明显上调了胶质原纤维酸性蛋白（GFAP），并且失去了许多正常原生质体星形胶质细胞基因和金属硫蛋白基因的表达。与对照样品中的星形胶质细胞相比，HD中的星形胶质细胞签名还显示出许多基因的表达下调，包括与原生质体星形胶质细胞功能和脂质合成相关的几个基因。因此，HD星形胶质细胞以可变的转录表型出现，并且可以分为几种不同的“状态”，由基因表达模式定义。最终，这项研究开始填补了HD中单细胞基因表达的知识空白，并提供了对星形胶质细胞对该疾病“反应”期间基因表达变化的更详细了解。