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Human VCP mutant ALS/FTD microglia display immune and lysosomal phenotypes independently of GPNMB

GSE282665 Homo sapiens (human) RNA-seq (gene expression) 93 samples Submitted 2024/12/09 Platform GPL16791
At a glance

RNA-seq (gene expression) · human · 93 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
93 samples: 91 distinct titles, 2 of them repeatedGroups 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.
Paper
Human VCP mutant ALS/FTD microglia display immune and lysosomal phenotypes independently of GPNMBMolecular neurodegeneration · 2024
Summary (written by the submitters)
Background: Microglia play crucial roles in mediating neuronal homeostasis but have been implicated in contributing to amyotrophic lateral sclerosis (ALS). However, the role of microglia in ALS remains incompletely understood. Methods: Here, we generated highly enriched cultures of VCP mutant microglia derived from human induced pluripotent stem cells (hiPSCs) to investigate their cell autonomous and non-cell autonomous roles in ALS pathogenesis.
Read the full summary ↓
We used RNA-sequencing, proteomics and functional assays to study hiPSC derived VCP mutant microglia and their effects on hiPSC derived motor neurons and astrocytes. Results: Transcriptomic, proteomic and functional analyses revealed immune and lysosomal dysfunction in VCP mutant microglia. Stimulating healthy microglia with inflammatory inducer lipopolysaccharide (LPS) showed partial overlap with VCP mutant microglia in their reactive transformation. LPS-stimulated VCP mutant microglia displayed differential activation of inflammatory pathways compared with LPS-stimulated healthy microglia. Conserved gene expression changes were identified between VCP mutant microglia, SOD1 mutant mice microglia, and postmortem ALS spinal cord microglial signatures, including increased expression of the transmembrane glycoprotein GPNMB. While knockdown of GPNMB affected inflammatory and phagocytosis processes in microglia, this was not sufficient to ameliorate cell autonomous phenotypes in VCP mutant microglia. Secreted factors from VCP mutant microglia were sufficient to activate the JAK-STAT pathway in hiPSC derived motor neurons and astrocytes. Conclusions: VCP mutant microglia undergo cell autonomous reactive transformation involving immune and lysosomal dysfunction that partially recapitulate key phenotypes of microglia from ALS models and post mortem tissue and are independent of GPNMB. VCP mutant microglia elicit non cell autonomous responses in motor neurons and astrocytes involving the JAK-STAT pathway.
Published in
Human VCP mutant ALS/FTD microglia display immune and lysosomal phenotypes independently of GPNMB
Clarke BE, Ziff OJ, Tyzack G et al. · Molecular neurodegeneration 2024 · PMID 39593143 · doi:10.1186/s13024-024-00773-1
This dataset
Open GSE282665 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 GSE282665_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 PRJNA1195017 and SRA study SRP549901. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39593143) ↗
Study design
91 distinct titles, 2 of them repeated
untx_ctrl ×2 lps_ctrl ×2

How we read this: Read from 93 sample titles: 91 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

+ 53 more — browse all 93 samples with per-sample file links →

Datasets on a similar topic

Search all human RNA-seq datasets in GEO →

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