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| Status |
Public on Feb 03, 2014 |
| Title |
Pathways Disrupted in Human ALS Motor Neurons Identified Through Genetic Correction of Mutant SOD1 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Although many distinct mutations in a variety of genes are known to cause Amyotrophic Lateral Sclerosis (ALS), it remains poorly understood how they selectively impact motor neuron biology and whether they converge on common pathways to cause neural degeneration. Here, we have combined reprogramming and stem cell differentiation approaches with genome engineering and RNA sequencing to define the transcriptional changes that are induced in human motor neurons by mutant SOD1. Mutant SOD1 protein induced a transcriptional signature indicative of increased oxidative stress, reduced mitochondrial function, altered sub-cellular transport as well as activation of the ER stress and unfolded protein response pathways. Functional studies demonstrated that perturbations in these pathways were indeed the source of altered transcript levels.
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| Overall design |
5 samples, 2 patient-derived SOD1A4V and 3 isogenic control samples where the mutation has been corrected. All samples are motor neurons derived from induced pluripotent stem cells (iPSCs), and isolated after lentiviral infection with an Hb9:RFP construct and FACS purification. Each sample is a separate biological replicate.
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| Contributor(s) |
Moccia R, Kiskinis E, Eggan K |
| Citation(s) |
24704492 |
| |
| Submission date |
Jan 27, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Kevin Eggan |
| Organization name |
Harvard University
|
| Department |
Stem Cell and Regenerative Biology
|
| Street address |
7 Divinity Avenue, Sherman Fairchild 258A
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02138 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA236453 |
| SRA |
SRP035862 |
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