Table 1.

Recent transcriptome studies of pathogenic mutations in RNA-mediated nonmotor neuron neurodegenerative diseases (HD and SCA)

Study	Samples	Platform	Measure of differential expression (no. differentially expressed)	Main findings
HD:
Jacobsen et al. [218]	RNA extracted from mouse embryonic stem cells expressing wild-type huntingtin with 7Q, and knock-in expansions of length 20Q, 50Q, 91Q and 111Q (n = 3–6 replicates per group).	Affymetrix Mouse 430A microarray	Correlation examined between expansion length and gene expression, Pearson coefficient > 0.8, P < 0.001 (25 probes positively correlated, 48 probes negatively correlated)	Genes correlated with expansion size distinct from genes dysregulated by knockdown of huntingtin, but are within similar functional pathways including energy and lipid metabolism.
Feyeux et al. [219]	RNA extracted from six embryonic stem cell and corresponding neural stem cell lines expressing huntingtin with 40–51Q expansions and four wild-type lines	Illumina Human WG-6 v3 microarray	Compared with wild type, Limma, P < 0.001 (embryonic stem cell: 163, neural stem cell: 66)	Dysregulated gene expression functionally enriched for energy and lipid metabolism and gene expression; no overlap with data sets analysing gene expression in brain tissue from symptomatic adults
Mattis et al. [220]	RNA extracted from neural stem cells and striatal neurons derived via induced pluripotent stem cells from patients with 60–180Q expansions of huntingtin and wild-type controls (n = 2–3 each group)	Human Affymetrix Exon 1.0 ST microarray.	Comparison to wild type, anova, FC > 2 (NSC: 1601; striatal neurons: not stated)	Neural stem cells: Dysregulated genes functionally enriched for signalling, cell cycle, axonal guidance and neural development. Some changes specific to longer or shorter repeat length. Striatal neurons: Dysregulated genes in striatal neurons functionally enriched for proliferation, signalling and cellular assembly
Soldati et al. [221]	RNA extracted from striatal neurons obtained and grown from mice expressing two huntingtin alleles with 109Q expansions, nonexpanded 7Q alleles.	Illumina MouseWG-6 v2.0 microarray	Compared with 7Q homozygous cells: Benjamini Hochberg, FDR < 0.02 (1013↑ and 1342↓)	Dysregulated genes functionally enriched for nervous system development and function. Down-regulated genes in these functional categories were enriched for REST binding sites.
Lewandowski et al. [222]	RNA extracted from posterior and anterior caudate, and S1 of patient (mean huntingtin expansion 41Q) and control brains (n = 10 each group)	Affymetrix Human U133A 2.0 microarray	Compared with control, repeat measures anova, controlling for region, P < 0.05 (3)	Focused on down-regulation of PPP1R7 which is implicated in neuronal function
Lee et al. [223]	RNA extracted from lymphoblastoid cell lines derived from 107 patients with huntingtin expansions of 15–92Q	Affymetrix Human U133A 2.0 microarray	Pearson correlation between probe expression and expansion length used to derive a biomarker of expansion length	Correlated genes involved in ribosomal function, transcription, nucleic acid metabolism, adhesion, energy metabolism, hormone response, synaptic transmission, neurological process
SCA7
Chou et al. [224]	RNA extracted from the cerebellum of symptomatic transgenic mice expressing human ataxin 7 with a 52Q expansion, and wild-type mice (n = 4 each group)	Affymetrix Mouse 430A microarray	Compared with wild type, t-test, P < 0.05, FC > 1.4 (10↑ and 34↓)	Down-regulated genes involved in neuronal function, protein processing, heat shock response and glial function. Up-regulated genes include RNA binding proteins.
Friedrich et al. [225]	RNA extracted from laser-captured Purkinje neurons from cerebellum of transgenic mice expressing human ataxin 7 with 90Q expansion and wild type mice	Affymetrix Mouse 430A microarray	P7E: Compared with wild type, FDR P < 0.2 (13)	Down-regulated genes involved in vulnerability to excitotoxicity.
SCA17
Ren et al. [226]	RNA extracted from heads of transgenic flies expressing human TBP with a 34Q or 80Q expansion, at days 5, 28 and 35. Day 28 is immediately prior to the onset of motor symptoms in the 80Q flies.	Affymetrix Drosophila Genome 2.0 microarray	Compared with 34Q samples at each time point, t-test, P < 0.05; FC > 1.4 (536)	Differentially expressed genes functionally enriched for pathways, including oxidation and mitochondrial function. Pearson correlation analysis implicated transcription factor Su(H) in control of dysregulated gene expression.
SCA2
Damrath et al. [227]	RNA extracted from cerebellum, brainstem and liver of transgenic mice expressing ataxin 2 with a 42Q expansion at 6 months (presymptomatic) and 18 months (symptomatic), and wild-type mice (n = 3–4 per group)	Affymetrix Mouse 430A microarray	Compared with wild type, Benjamini Hochberg (6 months: no significant gene expression changes. 18 months: cerebellum 20 genes; brainstem 14 genes, liver 30 genes)	In cerebellum, identified dysregulation of Adam1a and Fbxw8 which are neighbouring genes of ataxin 2. Fbxw8 implicated in neuronal dendrite formation
SCA3
Hsieh et al. [228]	RNA extracted from SK-N-SH cells engineered to stably express ataxin 3 with 26Q or 78Q expansion (n = 2 each group)	ABC Human UniversoChip 8k-1 microarray	Comparison with 26Q expressing cells, genes ranked by fold change	Most differentially expressed gene by fold change was CA11; function of CA11 unknown.
SCA28
Mancini et al. [229]	RNA extracted from lymophoblastoid cell lines derived from patients with mutations of AFG3L2 or matched controls (n = 4–6 each group)	Affymetrix Human U133A 2.0 microarray	Compared with controls, rank product, FDR < 0.005 (35↑ and 31↓)	Differentially expressed genes implicated in regulation of cell proliferation, cell death, cell adhesion, oxidative stress and chemical homeostasis

FC, fold change; FDR, false discovery rate; HD, Huntington's disease; SCA, spinocerebellar ataxia.