 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jan 15, 2019 |
| Title |
ALS implicated protein TDP-43 sustains levels of STMN2 a mediator of motor neuron growth and repair |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The discovery that TDP-43 mutations cause familial ALS and that many patients display pathological TDP-43 mislocalization has nominated altered RNA metabolism as a potential disease mechanism. Despite its importance, the identity of RNAs regulated by TDP-43 in motor neurons remains poorly understood. Here, we report transcripts whose abundances in human motor neurons are sensitive to TDP-43 depletion. Notably, we found STMN2, which encodes a microtubule regulator, declined after TDP-43 knockdown, in patient-specific motor neurons, following TDP-43 mislocalization, and in the postmortem patient spinal cords. Loss of STMN2 upon reduced TDP-43 function was due to the emergence of a cryptic exon, which is of substantial functional importance, as we further demonstrate that STMN2 is necessary for both axonal outgrowth and repair. Importantly, post-translational stabilization of STMN2 could rescue neurite outgrowth and axon regeneration deficits induced by TDP-43 depletion. We propose restoring STMN2 expression warrants future examination as an ALS therapeutic strategy.
|
| |
|
| Overall design |
Transcriptome differential expression analysis in HUES3 cells with and without siRNA knockdown of TDP-43
|
| |
|
| Contributor(s) |
Klim JR, Williams LA, Limone F, Guerra San Juan I, Davis-Dusenbery BN, Mordes DA, Burberry A, Steinbaugh MJ, Gamage KK, Kirchner R, Moccia R, Cassel S, Chen K, Wainger BJ, Wolff CJ, Eggan K |
| Citation(s) |
30643292 |
| |
| Submission date |
Oct 22, 2018 |
| Last update date |
Mar 27, 2019 |
| Contact name |
Rory Kirchner |
| E-mail(s) |
rory.kirchner@gmail.com
|
| Organization name |
Harvard T.H. Chan School of Public Health
|
| Department |
Department of Biostatistics
|
| Street address |
677 Huntington Ave
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (18)
|
|
| Relations |
| BioProject |
PRJNA497804 |
| SRA |
SRP166282 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE121569_category_als_vs_control_all.csv.gz |
3.7 Mb |
(ftp)(http) |
CSV |
| GSE121569_combined.dexseq.txt.gz |
9.7 Mb |
(ftp)(http) |
TXT |
| GSE121569_dexseq-all.csv.gz |
53.7 Mb |
(ftp)(http) |
CSV |
| GSE121569_raw_counts.csv.gz |
4.9 Mb |
(ftp)(http) |
CSV |
| GSE121569_tpm.csv.gz |
2.7 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...