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Alzheimer’s disease neuroinflammatory risk genes can be targeted with RNase-H active antisense oligonucleotides in human microglia

GSE219284 Mus musculus (mouse) RNA-seq (gene expression) 24 samples Submitted 2024/04/26 Platform GPL31277

At a glance

RNA-seq (gene expression) · mouse · 24 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: Mus musculus (mouse)
Samples: 24 samples
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: Regulation of human microglial gene expression and function via RNAase-H active antisense oligonucleotides in vivo in Alzheimer's diseaseMolecular neurodegeneration · 2024

Summary (written by the submitters)

Microglia play important roles in maintaining brain homeostasis. The discovery of genetic variants in the genes encoding Apolipoprotein E (APOE) and triggering receptor expressed on myeloid cells 2 (TREM2) as the strongest risk factors for Alzheimer’s disease (AD) highlights the importance of microglial biology in the brain. The sequence, structure and function of microglial proteins are poorly conserved across species, and this hampered the development of APOE and TREM2 targeting therapeutic strategies.

Read the full summary ↓

One way to target APOE and TREM2 is to modulate their expression using antisense oligonucleotides (ASOs). In this study, we identified ASOs that selectively and potently reduce human APOE and TREM2 levels in human myeloid cells including iPSC-derived microglia. We demonstrated that a single bolus delivery of the ASOs in the mouse cerebrospinal fluid (CSF) is sufficient for the ASO to be pharmacologically active and modify the phenotype of xenografted human microglia throughout the mouse brain for at least 4 weeks. This study is the first proof-of-concept that the expression of microglial genes can be modulated using ASOs in a dose-dependent manner in order to manipulate human microglia phenotypes in vivo, and demonstrates the utility of these ASOs both as research and therapeutic tools to modulate neuroinflammation.

Published in

Regulation of human microglial gene expression and function via RNAase-H active antisense oligonucleotides in vivo in Alzheimer's disease

Vandermeulen L, Geric I, Fumagalli L et al. · Molecular neurodegeneration 2024 · PMID 38654375 · doi:10.1186/s13024-024-00725-9

This dataset

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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 GSE219284_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 PRJNA907839 and SRA study SRP411096. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38654375) ↗

Samples in this study

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+ 24 more — browse all 24 samples with per-sample file links →

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