|
| Status |
Public on Jul 17, 2020 |
| Title |
Cell Type-Specific Transcriptomics Reveals that Mutant Huntingtin Leads to Mitochondrial RNA Release and Neuronal Innate Immune Activation |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The mechanisms by which mutant Huntingtin leads to neuronal cell death in Huntington’s disease are not fully understood. To gain new molecular insights, we used snRNA-Seq and TRAP to conduct transcriptomic analyses of striatal cell type-specific gene expression changes in human HD and mouse models of HD. In striatal spiny projection neurons we observe a release of mitochondrial RNA and a concomitant upregulation of innate immune signaling in spiny projection neurons. We observe that the released mtRNAs can directly bind to the innate immune sensor PKR. We highlight the importance of studying cell type-specific gene expression dysregulation in HD pathogenesis, and reveal that the activation of innate immune signaling in the most vulnerable HD neurons provides a novel framework to understand the basis of mHTT toxicity and raises new therapeutic opportunities.
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| |
|
| Overall design |
Cell type-specific profiling of human HD and HD mouse model striatal and corticostriatal cell types.
Please note that the additional counts.mtx, coldata.tsv and rowdata.tsv files containing metadata and sample information were provided on Oct 22, 2020.
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| |
|
| Contributor(s) |
Pineda SS, Lee H, Heiman M |
| Citation(s) |
32681824, 36650127 |
| |
| Submission date |
Jun 08, 2020 |
| Last update date |
Jan 18, 2023 |
| Contact name |
Myriam Heiman |
| E-mail(s) |
mheiman@mit.edu
|
| Organization name |
Massachusetts Institute of Technology
|
| Department |
Brain and Cognitive Sciences
|
| Lab |
Heiman
|
| Street address |
77 Massachusetts Ave., Bldg 46-4285
|
| City |
Cambridge |
| State/province |
Massachusetts |
| ZIP/Postal code |
02139 |
| Country |
USA |
| |
|
| Platforms (4)
|
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (333)
|
|
| Relations |
| BioProject |
PRJNA638165 |
| SRA |
SRP266498 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE152058_R62_snRNA_processed_coldata.tsv.gz |
646.2 Kb |
(ftp)(http) |
TSV |
| GSE152058_R62_snRNA_processed_counts.mtx.gz |
462.5 Mb |
(ftp)(http) |
MTX |
| GSE152058_R62_snRNA_processed_rowdata.tsv.gz |
244.7 Kb |
(ftp)(http) |
TSV |
| GSE152058_RAW.tar |
6.0 Gb |
(http)(custom) |
TAR (of MTX, TSV) |
| GSE152058_RPKM_R62_TRAP_CStrPN.tsv.gz |
2.3 Mb |
(ftp)(http) |
TSV |
| GSE152058_barcodes.tsv.gz |
18.5 Mb |
(ftp)(http) |
TSV |
| GSE152058_counts.STAR.MOUSE_3mo_D2.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE152058_counts.STAR.MOUSE_R62_D1_D2.txt.gz |
789.3 Kb |
(ftp)(http) |
TXT |
| GSE152058_counts_allelic_series_6mo.tsv.gz |
5.4 Mb |
(ftp)(http) |
TSV |
| GSE152058_features_GRCh38.tsv.gz |
264.3 Kb |
(ftp)(http) |
TSV |
| GSE152058_features_mm10.tsv.gz |
244.7 Kb |
(ftp)(http) |
TSV |
| GSE152058_human_snRNA_processed_coldata.tsv.gz |
792.9 Kb |
(ftp)(http) |
TSV |
| GSE152058_human_snRNA_processed_counts.mtx.gz |
847.7 Mb |
(ftp)(http) |
MTX |
| GSE152058_human_snRNA_processed_rowdata.tsv.gz |
264.3 Kb |
(ftp)(http) |
TSV |
| GSE152058_zQ175_snRNA_processed_coldata.tsv.gz |
364.5 Kb |
(ftp)(http) |
TSV |
| GSE152058_zQ175_snRNA_processed_counts.mtx.gz |
260.6 Mb |
(ftp)(http) |
MTX |
| GSE152058_zQ175_snRNA_processed_rowdata.tsv.gz |
244.7 Kb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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