GEO DataSets

(Submitter supplied) Huntington’s disease (HD) is an incurable neurodegenerative disorder that is caused by CAG trinucleotide expansions in the huntingtin gene. However, the exact molecular and cellular mechanisms underlying the pathogenesis of HD are still not well understood. Immune signaling has been hypothesized to contribute to HD pathogenesis. In this study, we used single-nucleus RNA sequencing (snRNA-seq) to access the transcriptional profiles of striatal cell types in control and R6/2 HD model mice that either had normal levels of, or were deficient for, the cytokine interleukin-6 (IL-6). more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

12 Samples

Download data: TAR

(Submitter supplied) We performed RNA-seq on head tissue collected from Drosophila expressing N-terminal (UAS-HTTNT231Q128) or full-length (UAS-HTTFL200Q) human mHTT in neurons (elav-GAL4) or glia (repo-GAL4).

Organism:

Drosophila melanogaster

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17275

72 Samples

Download data: TXT

(Submitter supplied) Huntington’s disease (HD) is a dominantly inherited neurodegenerative disorder caused by a trinucleotide expansion in exon 1 of the huntingtin (Htt) gene. Cell death in HD occurs primarily in striatal medium spiny neurons (MSNs), but the involvement of specific MSN subtypes and of other striatal cell types remains poorly understood. To gain insight into cell type-specific disease processes, we studied the nuclear transcriptomes of 4,524 cells from the striatum of a genetically precise knock-in mouse model of the HD mutation, HttQ175/+, and from wildtype controls. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21103

7 Samples

Download data: CSV, TXT

(Submitter supplied) We report the gene expression alterations observed in freshly isolated microglia from the striatum 10-month-old Q175 mice with and without Tyrobp

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

18 Samples

Download data: TXT

(Submitter supplied) We report the gene expression alterations observed in the striatum 10-month-old Q175 mice with and without Tyrobp

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

24 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by array

Platforms:

GPL81 GPL1261

32 Samples

Download data: CEL

(Submitter supplied) Achieving a mechanistic understanding of disease and initiating preclinical therapeutic trials necessitate the study of huntingtin toxicity and its remedy in model systems. To allow the engagement of appropriate experimental paradigms, Huntington’s disease (HD) models need to be validated in terms of how they recapitulate a particular aspect of human disease. In order to examine transcriptome-related effects of mutant huntingtin, we compared striatal mRNA profiles from seven genetic mouse models of disease to that of postmortem human HD caudate using microarray analysis. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

8 Samples

Download data: CEL

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

18 Samples

Download data: CEL

(Submitter supplied) To test the hypotheses that mutant huntingtin protein length and wild-type huntingtin dosage have important effects on disease-related transcriptional dysfunction, we compared the changes in mRNA in seven genetic mouse models of Huntington's disease (HD) and postmortem human HD caudate. Transgenic models expressing short N-terminal fragments of mutant huntingtin (R6/1 and R6/2 mice) exhibited the most rapid effects on gene expression, consistent with previous studies. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

9 Samples

Download data: CEL

(Submitter supplied) To test the hypotheses that mutant huntingtin protein length and wild-type huntingtin dosage have important effects on disease-related transcriptional dysfunction, we compared the changes in mRNA in seven genetic mouse models of Huntington's disease (HD) and postmortem human HD caudate. Transgenic models expressing short N-terminal fragments of mutant huntingtin (R6/1 and R6/2 mice) exhibited the most rapid effects on gene expression, consistent with previous studies. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

9 Samples

Download data: CEL

(Submitter supplied) To test the hypotheses that mutant huntingtin protein length and wild-type huntingtin dosage have important effects on disease-related transcriptional dysfunction, we compared the changes in mRNA in seven genetic mouse models of Huntington's disease (HD) and postmortem human HD caudate. Transgenic models expressing short N-terminal fragments of mutant huntingtin (R6/1 and R6/2 mice) exhibited the most rapid effects on gene expression, consistent with previous studies. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL81

6 Samples

Download data: CEL

(Submitter supplied) Achieving a mechanistic understanding of disease and initiating preclinical therapeutic trials necessitate the study of huntingtin toxicity and its remedy in model systems. To allow the engagement of appropriate experimental paradigms, Huntington’s disease (HD) models need to be validated in terms of how they recapitulate a particular aspect of human disease. In order to examine transcriptome-related effects of mutant huntingtin, we compared striatal mRNA profiles from seven genetic mouse models of disease to that of postmortem human HD caudate using microarray analysis. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL1261

12 Samples

Download data: CEL

(Submitter supplied) Huntington’s disease (HD), caused by a CAG repeat expansion in the huntingtin (HTT) gene, is characterized by abnormal protein aggregates and motor and cognitive dysfunction. Htt protein is ubiquitously expressed, but the striatal medium spiny neuron (MSN) is most susceptible to neuronal dysfunction and death. Abnormal gene expression represents a core pathogenic feature of HD, but the relative roles of cell-autonomous and non-cell-autonomous effects on transcription remain unclear. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6885

7 Samples

Download data: TXT

(Submitter supplied) Huntington disease (HD) is a fatal neurodegenerative disorder without cure, caused by an aberrant expansion of CAG repeats in the exon 1 of the Huntingtin (HTT) gene. Although the negative correlation between the number of CAG repeats and the age of disease onset is well established, additional factors may contribute to the high heterogeneity in the complex manifestation of the symptoms among patients. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

16 Samples

Download data: TXT

(Submitter supplied) Long-term implantation of human NSCs in Huntington’s disease (HD) mice ameliorates behavioral deficits and reduces mutant Huntingtin accumulation. The human NSCs survive and differentiate into diverse neuronal populations, form connections, improve synaptic properties and show restoration of several transcriptional changes in HD mouse cells.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

1 Sample

Download data: CSV, XLSX

(Submitter supplied) Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease whose predominant neuropathological signature is the selective loss of medium spiny neurons in the striatum.  Despite this selective neuropathology, the mutant protein (huntingtin) is found in virtually every cell so far studied, and, consequently, phenotypes are observed in a wide range of organ systems both inside and outside the central nervous system. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

35 Samples

Download data: CSV

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

34 Samples

Download data: BW

(Submitter supplied) Huntington’s disease (HD) is a chronic neurodegenerative disorder characterized by a late clinical onset despite ubiquitous expression of the mutant Huntingtin gene (HTT) from birth. Transcriptional dysregulation is a pivotal feature of HD. Yet, the genes that are altered in the prodromal period and their regulators, which present opportunities for therapeutic intervention, remain to be elucidated. Using transcriptional and chromatin profiling, we found aberrant transcription and changes in histone H3K27 acetylation in the striatum of R6/1 mice during the presymptomatic disease stages. Integrating these data, we identified the Elk-1 transcription factor as a candidate regulator of prodromal changes in HD. Exogenous expression of Elk-1 exerted beneficial effects in a primary striatal cell culture model of HD, and adeno-associated virus-mediated Elk-1 overexpression alleviated transcriptional dysregulation in R6/1 mice. Collectively, our work demonstrates that aberrant gene expression precedes overt disease onset in HD, identifies the Elk-1 transcription factor as a key regulator linked to early epigenetic and transcriptional changes in HD, and presents evidence for Elk-1 as a target for alleviating molecular pathology in HD.

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

8 Samples

Download data: BW

(Submitter supplied) Huntington’s disease (HD) is a chronic neurodegenerative disorder characterized by a late clinical onset despite ubiquitous expression of the mutant Huntingtin gene (HTT) from birth. Transcriptional dysregulation is a pivotal feature of HD. Yet, the genes that are altered in the prodromal period and their regulators, which present opportunities for therapeutic intervention, remain to be elucidated. Using transcriptional and chromatin profiling, we found aberrant transcription and changes in histone H3K27 acetylation in the striatum of R6/1 mice during the presymptomatic disease stages. Integrating these data, we identified the Elk-1 transcription factor as a candidate regulator of prodromal changes in HD. Exogenous expression of Elk-1 exerted beneficial effects in a primary striatal cell culture model of HD, and adeno-associated virus-mediated Elk-1 overexpression alleviated transcriptional dysregulation in R6/1 mice. Collectively, our work demonstrates that aberrant gene expression precedes overt disease onset in HD, identifies the Elk-1 transcription factor as a key regulator linked to early epigenetic and transcriptional changes in HD, and presents evidence for Elk-1 as a target for alleviating molecular pathology in HD.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

26 Samples

Download data: TXT

(Submitter supplied) Selective degeneration of striatal projection neurons is one of the main features of Huntington’s disease (HD). The differences between vulnerable and resilient striatal cell types and cell type-specific molecular events associated with HD progression have not been established. Here we employed fluorescence-activated nuclear sorting (FANS) and deep molecular profiling to gain insight into the properties of different cell types of the human striatum in HD and control donors.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24676

344 Samples

Download data: BW, TXT