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GSE121569

GSE GEO
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ALS implicated protein TDP-43 sustains levels of STMN2 a mediator of motor neuron growth and repair

Organism: Homo sapiens
Platform: GPL11154
Samples: 18
Experiment Types:
Expression profiling by high throughput sequencing
Submitted: Oct 22 2018
Last Updated: Mar 27 2019
Status: Public on Jan 15 2019
Contact: Rory,,Kirchner (Harvard T.H. Chan School of Public Health)

Relations

BioProject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA497804 SRA: https://www.ncbi.nlm.nih.gov/sra?term=SRP166282

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

Analysis (12 steps)

View Data Processing
Processing steps for GSE121569
  1. All FASTQ files were analyzed using the bcbioRNASeq workflow and toolchain91.
  2. The FASTQ files were aligned to the GRCh37/hg19 reference genome.
  3. Differential expression testing was performed using DESeq2 suite of bioinformatics tools38.
  4. The DEXSeq module of Bioconductor was used to identify differential splicing92.
  5. We used salmon to generate the counts and tximport to load them at gene level93,94.
  6. All p-values are then corrected for multiple comparisons using the method of Benjamini and Hochberg95.
  7. We used an adjusted p-value cutoff of 0.05 with no log fold-change ratio cutoff for differential gene expression analysis and a 0.1 cutoff with no log fold-change ratio cutoff for differential exon usage.
  8. [tpm.csv.gz] gene x sample matrix of TPM for each sample
Showing first 8 steps.

Supplementary Files (5)

GSE121569_category_als_vs_control_all.csv.gz Download
GSE121569_combined.dexseq.txt.gz Download
GSE121569_dexseq-all.csv.gz Download
GSE121569_raw_counts.csv.gz Download
GSE121569_tpm.csv.gz Download
GEO Samples (18)
GSM3439289 GSM3439290 GSM3439291 GSM3439292 GSM3439293 GSM3439294 GSM3439295 GSM3439296 GSM3439297 GSM3439298 GSM3439299 GSM3439300 GSM3439301 GSM3439302 GSM3439303 GSM3439304 GSM3439305 GSM3439306

Dataset Citations (1)

PubMed citation (PMID 30643292)

SRA Experiments (18) and Runs (18)

Total: 44154 MB
SRX4910907 SRP166282 RNA-Seq PAIRED
GSM3439289: fluorescent siRNA rep1; Homo sapiens; RNA-Seq
Sample: SRS3956633
BioProject: PRJNA497804
BioSample: SAMN10266570
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: fluorescent siRNA, differentiated HUES3 into hMNs
cell type: differentiated HUES3 into hMNs
sirna type: fluorescent
genotype: control
date: 2013-01-10
Original files (1)
fluorescent siRNA, differentiated HUES3 into hMNs
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR8083864 36338577 5523463704 3761.26 BD_09_1.fastq.gz, BD_09_2.fastq.gz, SRR8083864, SRR8083864.sralite SRA
SRX4910908 SRP166282 RNA-Seq PAIRED
GSM3439290: scramble siRNA rep1; Homo sapiens; RNA-Seq
Sample: SRS3956634
BioProject: PRJNA497804
BioSample: SAMN10266569
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: scramble siRNA, differentiated HUES3 into hMNs
cell type: differentiated HUES3 into hMNs
sirna type: scramble
genotype: control
date: 2013-01-10
Original files (1)
scramble siRNA, differentiated HUES3 into hMNs
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR8083865 41466605 6302923960 4270.25 BD_10_2.fastq.gz, SRR8083865, SRR8083865.sralite, BD_10_1.fastq.gz SRA
SRX4910909 SRP166282 RNA-Seq PAIRED
GSM3439291: scramble siRNA rep2; Homo sapiens; RNA-Seq
Sample: SRS3956635
BioProject: PRJNA497804
BioSample: SAMN10266568
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: scramble siRNA, differentiated HUES3 into hMNs
cell type: differentiated HUES3 into hMNs
sirna type: scramble
genotype: control
date: 2013-01-10
Original files (1)
scramble siRNA, differentiated HUES3 into hMNs
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR8083866 33278121 5058274392 3454.8 BD_11_1.fastq.gz, BD_11_2.fastq.gz, SRR8083866, SRR8083866.sralite SRA
SRX4910910 SRP166282 RNA-Seq PAIRED
GSM3439292: TDP43 siRNA rep1; Homo sapiens; RNA-Seq
Sample: SRS3956636
BioProject: PRJNA497804
BioSample: SAMN10266567
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: TDP43 siRNA, differentiated HUES3 into hMNs
cell type: differentiated HUES3 into hMNs
sirna type: TDP43
genotype: TDP43 knockdown
date: 2013-01-10
Original files (1)
TDP43 siRNA, differentiated HUES3 into hMNs
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR8083867 57329553 8714092056 5939.85 BD_12_2.fastq.gz, SRR8083867, SRR8083867.sralite, BD_12_1.fastq.gz SRA
SRX4910911 SRP166282 RNA-Seq PAIRED
GSM3439293: TDP43 siRNA rep2; Homo sapiens; RNA-Seq
Sample: SRS3956637
BioProject: PRJNA497804
BioSample: SAMN10266566
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: TDP43 siRNA, differentiated HUES3 into hMNs
cell type: differentiated HUES3 into hMNs
sirna type: TDP43
genotype: TDP43 knockdown
date: 2013-01-10
Original files (1)
TDP43 siRNA, differentiated HUES3 into hMNs
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR8083868 39231704 5963219008 4060.81 BD_13_1.fastq.gz, BD_13_2.fastq.gz, SRR8083868, SRR8083868.sralite SRA
SRX4910912 SRP166282 RNA-Seq PAIRED
GSM3439294: no siRNA rep1; Homo sapiens; RNA-Seq
Sample: SRS3956638
BioProject: PRJNA497804
BioSample: SAMN10266565
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: no siRNA, differentiated HUES3 into hMNs
cell type: differentiated HUES3 into hMNs
sirna type: none
genotype: control
date: 2013-01-10
Original files (1)
no siRNA, differentiated HUES3 into hMNs
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR8083869 29517832 4486710464 2948.49 BD_19_1.fastq.gz, BD_19_2.fastq.gz, SRR8083869, SRR8083869.sralite SRA
SRX4910913 SRP166282 RNA-Seq PAIRED
GSM3439295: no siRNA rep2; Homo sapiens; RNA-Seq
Sample: SRS3956639
BioProject: PRJNA497804
BioSample: SAMN10266564
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: no siRNA, differentiated HUES3 into hMNs
cell type: differentiated HUES3 into hMNs
sirna type: none
genotype: control
date: 2013-06-10
Original files (1)
no siRNA, differentiated HUES3 into hMNs
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR8083870 21010237 3193556024 1936.66 BD_20_1.fastq.gz, BD_20_2.fastq.gz, SRR8083870, SRR8083870.sralite SRA
SRX4910914 SRP166282 RNA-Seq PAIRED
GSM3439296: fluorescent siRNA rep2; Homo sapiens; RNA-Seq
Sample: SRS3956640
BioProject: PRJNA497804
BioSample: SAMN10266563
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: fluorescent siRNA, differentiated HUES3 into hMNs
cell type: differentiated HUES3 into hMNs
sirna type: fluorescent
genotype: control
date: 2013-06-10
Original files (1)
fluorescent siRNA, differentiated HUES3 into hMNs
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR8083871 28057068 4264674336 2597.88 BD_21_1.fastq.gz, BD_21_2.fastq.gz, SRR8083871, SRR8083871.sralite SRA
SRX4910915 SRP166282 RNA-Seq PAIRED
GSM3439297: scramble siRNA rep3; Homo sapiens; RNA-Seq
Sample: SRS3956641
BioProject: PRJNA497804
BioSample: SAMN10266562
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: scramble siRNA, differentiated HUES3 into hMNs
cell type: differentiated HUES3 into hMNs
sirna type: scramble
genotype: control
date: 2013-06-10
Original files (1)
scramble siRNA, differentiated HUES3 into hMNs
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR8083872 25205022 3831163344 2312.53 BD_22_1.fastq.gz, BD_22_2.fastq.gz, SRR8083872, SRR8083872.sralite SRA
SRX4910916 SRP166282 RNA-Seq PAIRED
GSM3439298: scramble siRNA rep4; Homo sapiens; RNA-Seq
Sample: SRS3956642
BioProject: PRJNA497804
BioSample: SAMN10266561
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: scramble siRNA, differentiated HUES3 into hMNs
cell type: differentiated HUES3 into hMNs
sirna type: scramble
genotype: control
date: 2013-06-10
Original files (1)
scramble siRNA, differentiated HUES3 into hMNs
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR8083873 17669950 2685832400 1645.33 BD_23_1.fastq.gz, BD_23_2.fastq.gz, SRR8083873, SRR8083873.sralite SRA
SRX4910917 SRP166282 RNA-Seq PAIRED
GSM3439299: TDP43 siRNA rep3; Homo sapiens; RNA-Seq
Sample: SRS3956644
BioProject: PRJNA497804
BioSample: SAMN10266560
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: TDP43 siRNA, differentiated HUES3 into hMNs
cell type: differentiated HUES3 into hMNs
sirna type: TDP43
genotype: TDP43 knockdown
date: 2013-06-10
Original files (1)
TDP43 siRNA, differentiated HUES3 into hMNs
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR8083874 20498949 3115840248 1909.02 BD_24_1.fastq.gz, BD_24_2.fastq.gz, SRR8083874, SRR8083874.sralite SRA
SRX4910918 SRP166282 RNA-Seq PAIRED
GSM3439300: TDP43 siRNA rep4; Homo sapiens; RNA-Seq
Sample: SRS3956643
BioProject: PRJNA497804
BioSample: SAMN10266559
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: TDP43 siRNA, differentiated HUES3 into hMNs
cell type: differentiated HUES3 into hMNs
sirna type: TDP43
genotype: TDP43 knockdown
date: 2013-06-10
Original files (1)
TDP43 siRNA, differentiated HUES3 into hMNs
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR8083875 18881604 2870003808 1730.27 BD_25_1.fastq.gz, BD_25_2.fastq.gz, SRR8083875, SRR8083875.sralite SRA
SRX4910919 SRP166282 RNA-Seq PAIRED
GSM3439301: no siRNA rep3; Homo sapiens; RNA-Seq
Sample: SRS3956645
BioProject: PRJNA497804
BioSample: SAMN10266558
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: no siRNA, differentiated HUES3 into hMNs
cell type: differentiated HUES3 into hMNs
sirna type: none
genotype: control
date: 2013-06-10
Original files (1)
no siRNA, differentiated HUES3 into hMNs
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR8083876 12255415 1862823080 1088.31 BD_30_1.fastq.gz, BD_30_2.fastq.gz, SRR8083876, SRR8083876.sralite SRA
SRX4910920 SRP166282 RNA-Seq PAIRED
GSM3439302: fluorescent siRNA rep3; Homo sapiens; RNA-Seq
Sample: SRS3956646
BioProject: PRJNA497804
BioSample: SAMN10266557
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: fluorescent siRNA, differentiated HUES3 into hMNs
cell type: differentiated HUES3 into hMNs
sirna type: fluorescent
genotype: control
date: 2013-06-10
Original files (1)
fluorescent siRNA, differentiated HUES3 into hMNs
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR8083877 15270757 2321155064 1351.2 BD_31_1.fastq.gz, BD_31_2.fastq.gz, SRR8083877, SRR8083877.sralite SRA
SRX4910921 SRP166282 RNA-Seq PAIRED
GSM3439303: scramble siRNA rep5; Homo sapiens; RNA-Seq
Sample: SRS3956647
BioProject: PRJNA497804
BioSample: SAMN10266556
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: scramble siRNA, differentiated HUES3 into hMNs
cell type: differentiated HUES3 into hMNs
sirna type: scramble
genotype: control
date: 2013-06-10
Original files (1)
scramble siRNA, differentiated HUES3 into hMNs
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR8083878 15903552 2417339904 1411.39 BD_32_1.fastq.gz, BD_32_2.fastq.gz, SRR8083878, SRR8083878.sralite SRA
SRX4910922 SRP166282 RNA-Seq PAIRED
GSM3439304: scramble siRNA rep6; Homo sapiens; RNA-Seq
Sample: SRS3956649
BioProject: PRJNA497804
BioSample: SAMN10266555
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: scramble siRNA, differentiated HUES3 into hMNs
cell type: differentiated HUES3 into hMNs
sirna type: scramble
genotype: control
date: 2013-06-10
Original files (1)
scramble siRNA, differentiated HUES3 into hMNs
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR8083879 13516360 2054486720 1208.19 BD_33_1.fastq.gz, BD_33_2.fastq.gz, SRR8083879, SRR8083879.sralite SRA
SRX4910923 SRP166282 RNA-Seq PAIRED
GSM3439305: TDP43 siRNA rep5; Homo sapiens; RNA-Seq
Sample: SRS3956648
BioProject: PRJNA497804
BioSample: SAMN10266554
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: TDP43 siRNA, differentiated HUES3 into hMNs
cell type: differentiated HUES3 into hMNs
sirna type: TDP43
genotype: TDP43 knockdown
date: 2013-06-10
Original files (1)
TDP43 siRNA, differentiated HUES3 into hMNs
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR8083880 14259398 2167428496 1274.52 BD_34_1.fastq.gz, BD_34_2.fastq.gz, SRR8083880, SRR8083880.sralite SRA
SRX4910924 SRP166282 RNA-Seq PAIRED
GSM3439306: TDP43 siRNA rep6; Homo sapiens; RNA-Seq
Sample: SRS3956650
BioProject: PRJNA497804
BioSample: SAMN10266553
Platform: ILLUMINA
Instrument: Illumina HiSeq 2000
Organism: Homo sapiens
Sample attributes
source_name: TDP43 siRNA, differentiated HUES3 into hMNs
cell type: differentiated HUES3 into hMNs
sirna type: TDP43
genotype: TDP43 knockdown
date: 2013-06-10
Original files (1)
TDP43 siRNA, differentiated HUES3 into hMNs
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR8083881 14167853 2153513656 1252.84 BD_35_1.fastq.gz, BD_35_2.fastq.gz, SRR8083881, SRR8083881.sralite SRA

Linked Publications (1)

Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis.
Acta neuropathologica · 2022

Data Files (18)

Accession File Name Stored Type Output Type Mapping Assembly Size Download
— BD_09_1.fastq.gz RNA-Seq 3.7 GB link
— BD_10_2.fastq.gz RNA-Seq 4.2 GB link
— BD_11_1.fastq.gz RNA-Seq 3.4 GB link
— BD_12_2.fastq.gz RNA-Seq 5.8 GB link
— BD_13_1.fastq.gz RNA-Seq 4.0 GB link
— BD_19_1.fastq.gz RNA-Seq 2.9 GB link
— BD_20_1.fastq.gz RNA-Seq 1.9 GB link
— BD_21_1.fastq.gz RNA-Seq 2.5 GB link
— BD_22_1.fastq.gz RNA-Seq 2.3 GB link
— BD_23_1.fastq.gz RNA-Seq 1.6 GB link
— BD_24_1.fastq.gz RNA-Seq 1.9 GB link
— BD_25_1.fastq.gz RNA-Seq 1.7 GB link
— BD_30_1.fastq.gz RNA-Seq 1.1 GB link
— BD_31_1.fastq.gz RNA-Seq 1.3 GB link
— BD_32_1.fastq.gz RNA-Seq 1.4 GB link
— BD_33_1.fastq.gz RNA-Seq 1.2 GB link
— BD_34_1.fastq.gz RNA-Seq 1.2 GB link
— BD_35_1.fastq.gz RNA-Seq 1.2 GB link