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Alzheimer's disease-associated PLCG2 variants alter microglial state and function in human iPSC-derived microglia-like cells

GSE308813 Homo sapiens (human) RNA-seq (gene expression) 16 samples Submitted 2025/10/09 Platform GPL34284
At a glance

RNA-seq (gene expression) · human · 16 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
16 samples: 4 × Microglia, WT, Basal, vs 4 × Microglia, PLCG2 KO, Basal, vs 4 × Microglia, PLCG2 M28L, Basal, vs 4 × Microglia, PLCG2 P522R, Basal,Groups 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
Alzheimer's disease-associated PLCG2 variants alter microglial state and function in human induced pluripotent stem cell-derived microglia-like cellsAlzheimer's & dementia : the journal of the Alzheimer's Association · 2025
Summary (written by the submitters)
BACKGROUND: Variants of PLCG2, a key microglial immune signaling protein, are genetically linked to Alzheimer’s disease (AD) risk. Understanding how PLCG2 variants alter microglial function is critical for identifying mechanisms that drive neurodegeneration or resiliency in AD. METHODS: iPSC-derived microglia carrying the protective PLCG2P522R or risk-conferring PLCG2M28L variants, or loss of PLCG2, were generated to ascertain the impact on microglial transcriptome and function.
Read the full summary ↓
RESULTS: Protective PLCG2P522R microglia showed significant transcriptomic similarity to isogenic controls. In contrast, risk-conferring PLCG2M28L microglia shared similarities with PLCG2KO microglia, with functionally reduced TREM2 expression, blunted inflammatory responses, and increased proliferation and cell death. Uniquely, PLCG2P522R microglia showed elevated cytokine secretion after LPS stimulation and were protected from apoptosis. DISCUSSION: These findings demonstrate that PLCG2 variants drive distinct microglia transcriptomes that influence microglial functional responses that could contribute to AD risk and protection. Targeting PLCG2-mediated signaling may represent a powerful therapeutic strategy to modulate neuroinflammation.
Published in
Alzheimer's disease-associated PLCG2 variants alter microglial state and function in human induced pluripotent stem cell-derived microglia-like cells
Bedford LM, Tutrow KD, Hooper K et al. · Alzheimer's & dementia : the journal of the Alzheimer's Association 2025 · PMID 41066163 · doi:10.1002/alz.70772
This dataset
Open GSE308813 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 GSE308813_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 PRJNA1332737 and SRA study SRP625336. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41066163) ↗
Study design
4 × Microglia, WT, Basal, vs 4 × Microglia, PLCG2 KO, Basal, vs 4 × Microglia, PLCG2 M28L, Basal, vs 4 × Microglia, PLCG2 P522R, Basal,

Supports a between-group comparison across 16 samples.

How we read this: 4 replicated groups read from 16 sample titles; they account for 16 of them. 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
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