GEO series

Transcriptomic characterization of in vitro human iPSC-derived motor neuron systems for the exploration of cell autonomous mechanisms and modifiers of TDP-43 perturbation associated neurotoxicity

GSE261875 Homo sapiens (human) RNA-seq (gene expression) 32 samples Submitted 2024/03/23 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 32 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Homo sapiens (human)
Samples: 32 samples: 32 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.

Summary (written by the submitters)

Transactive Response DNA-binding protein 43 (TDP-43) is a multifunctional nuclear protein ubiquitously expressed in all tissues. Although it is primarily nuclear, Amyotrophic Lateral Sclerosis (ALS) patients frequently present with cytoplasmic aggregates of TDP-43 in motor neurons on post-mortem examination. Although only about 5% of all ALS patients have a TARDBP mutation (Ghasemi and Brown 2018; Ingre et al.

Read the full summary ↓

2015), which is known to cause these insoluble cytoplasmic aggregates, 97% of ALS patients will develop cytoplasmic, insoluble TDP-43 aggregates regardless of whether they have a mutation in TARDBP or not (Ling et al. 2013). Overexpression of wild-type TDP-43 has previously been shown to be a valid model of inducing neurotoxicity as well as a limited amount of cytoplasmic re-localization and aggregation characteristic of ALS (Elden et al. 2010; Wils et al. 2010). In the search for modifiers of toxicity as conferred by TDP-43 overexpression in these models, knockout of Ataxin-2 (ATXN2) was proposed as a protective intervention in the context of TDP-43 perturbation in non-human model systems (Elden et al. 2010, Becker et al. 2017). This promising finding had not previously been validated in a human motor neuron system, nor had a thorough investigation been conducted to determine the mechanism of neuroprotection that ATXN2 knockout employs to drive the therapeutic effect. This sequencing study examines both ATXN2 intact and ATXN2 knockout motor neurons in the context of TDP-43 perturbation to explore global transcriptomic changes that arise from these changes in cellular state that are associated with progression of ALS (ATXN2 intact) and what pathways could be implicated in protection from ALS-associated neurodegeneration (ATXN2 Knockout).

This dataset

Open GSE261875 in finder → Find more human RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE261875_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1089256 and SRA study SRP496259. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

32 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 32 sample titles: 32 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8153370 Motor Neuron, Empty Vector Unpreturbed, Day 12, Bio Rep 1 [EV1]
GSM8153371 Motor Neuron, Empty Vector Unpreturbed, Day 12, Bio Rep 2 [EV2]
GSM8153372 Motor Neuron, Empty Vector Unpreturbed, Day 12, Bio Rep 3 [EV3]
GSM8153373 Motor Neuron, Empty Vector Unpreturbed, Day 12, Bio Rep 4 [EV4]
GSM8153374 Motor Neuron, YFP only, Day 12, Bio Rep 1 [Y1]
GSM8153375 Motor Neuron, YFP only, Day 12, Bio Rep 2 [Y2]
GSM8153376 Motor Neuron, YFP only, Day 12, Bio Rep 3 [Y3]
GSM8153377 Motor Neuron, YFP only, Day 12, Bio Rep 4 [Y4]
GSM8153378 Motor Neuron, TDP-43:YFP Overexpression, Day 12, Bio Rep 1 [T1]
GSM8153379 Motor Neuron, TDP-43:YFP Overexpression, Day 12, Bio Rep 2 [T2]
GSM8153380 Motor Neuron, TDP-43:YFP Overexpression, Day 12, Bio Rep 3 [T3]
GSM8153381 Motor Neuron, TDP-43:YFP Overexpression, Day 12, Bio Rep 4 [T4]
GSM8153382 Motor Neuron, TDP-43ΔNLS:YFP Overexpression, Day 12, Bio Rep 1 [N1]
GSM8153383 Motor Neuron, TDP-43ΔNLS:YFP Overexpression, Day 12, Bio Rep 2 [N2]
GSM8153384 Motor Neuron, TDP-43ΔNLS:YFP Overexpression, Day 12, Bio Rep 3 [N3]
GSM8153385 Motor Neuron, TDP-43ΔNLS:YFP Overexpression, Day 12, Bio Rep 4 [N4]
GSM8153386 Motor Neuron, Empty Vector ATXN2 Knockout, Day 12, Bio Rep 1 [EV_AKO1]
GSM8153387 Motor Neuron, Empty Vector ATXN2 Knockout, Day 12, Bio Rep 2 [EV_AKO2]
GSM8153388 Motor Neuron, Empty Vector ATXN2 Knockout, Day 12, Bio Rep 3 [EV_AKO3]
GSM8153389 Motor Neuron, Empty Vector ATXN2 Knockout, Day 12, Bio Rep 4 [EV_AKO4]
GSM8153390 Motor Neuron, YFP ATXN2 Knockout, Day 12, Bio Rep 1 [Y_AKO1]
GSM8153391 Motor Neuron, YFP ATXN2 Knockout, Day 12, Bio Rep 2 [Y_AKO2]
GSM8153392 Motor Neuron, YFP ATXN2 Knockout, Day 12, Bio Rep 3 [Y_AKO3]
GSM8153393 Motor Neuron, YFP ATXN2 Knockout, Day 12, Bio Rep 4 [Y_AKO4]
GSM8153394 Motor Neuron, TDP-43:YFP ATXN2 Knockout, Day 12, Bio Rep 1 [T_AKO1]
GSM8153395 Motor Neuron, TDP-43:YFP ATXN2 Knockout, Day 12, Bio Rep 2 [T_AKO2]
GSM8153396 Motor Neuron, TDP-43:YFP ATXN2 Knockout, Day 12, Bio Rep 3 [T_AKO3]
GSM8153397 Motor Neuron, TDP-43:YFP ATXN2 Knockout, Day 12, Bio Rep 4 [T_AKO4]
GSM8153398 Motor Neuron, TDP-43ΔNLS:YFP ATXN2 Knockout, Day 12, Bio Rep 1 [N_AKO1]
GSM8153399 Motor Neuron, TDP-43ΔNLS:YFP ATXN2 Knockout, Day 12, Bio Rep 2 [N_AKO2]
GSM8153400 Motor Neuron, TDP-43ΔNLS:YFP ATXN2 Knockout, Day 12, Bio Rep 3 [N_AKO3]
GSM8153401 Motor Neuron, TDP-43ΔNLS:YFP ATXN2 Knockout, Day 12, Bio Rep 4 [N_AKO4]

Datasets on a similar topic

GSE334500 Psychotropic-drug and neurotransmitter perturbation RNA-seq of human iPSC-derived cardiac and retinal organoids (ToxiPred) 96 samples shares ipsc-derived, perturbation
GSE263372 Efficient and reproducible generation of human iPSC-derived cardiomyocytes and cardiac organoids in stirred suspension systems 5 samples shares ipsc-derived, systems
GSE282668 TGF-β signaling promotes astroglial activation and TDP-43 proteinopathy in organoid models of frontotemporal lobar degeneration 54 samples shares tdp-43
GSE307054 Inhibition of nonsense-mediated decay in TDP-43 deficient neurons reveals novel cryptic exons 22 samples shares tdp-43
GSE304550 ALS-Associated TDP-43 Dysfunction Compromises UPF1-Dependent mRNA Metabolism Pathways Including Alternative Polyadenylation and 3’UTR Length 16 samples shares tdp-43
GSE296714 TDP-43 loss induces cryptic polyadenylation in ALS/FTD [humphrey-i3-cortical] 12 samples shares tdp-43
GSE212630 pTDP-43 levels correlate with cell type specific molecular alterations in the prefrontal cortex of C9orf72 ALS/FTD patients 52 samples shares tdp-43
GSE298758 DCPS modulates TDP-43 mediated neurodegeneration through P-body regulation [RNA-seq] 36 samples shares tdp-43

Search all human RNA-seq datasets in GEO →

Share this dataset

Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.