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Osteopontin drives neuroinflammation and cell loss in MAPT-N279K frontotemporal dementia patient neurons

GSE230450 Homo sapiens (human) Single-nucleus RNA-seq 22 samples Submitted 2024/04/15 Platform GPL24676
At a glance

Single-nucleus RNA-seq · human · 22 samples

What it is
Single-nucleus RNA-seqGene activity measured in individual nuclei (used when whole cells are hard to isolate, for example from frozen tissue). Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Homo sapiens (human)
Samples
22 samples: 6 conditions, mostly with about 4 replicates eachGroups 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
Osteopontin drives neuroinflammation and cell loss in MAPT-N279K frontotemporal dementia patient neuronsCell stem cell · 2024
Summary (written by the submitters)
Frontotemporal dementia (FTD) is an incurable group of early-onset dementias that can be caused by deposition of hyperphosphorylated tau in patient brains. However, the mechanisms leading to neurodegeneration remain largely unknown. Here, we combined single-cell analyses of FTD patient brains with a stem cell culture and transplantation model of FTD.
Read the full summary ↓
We identified disease phenotypes in FTD neurons carrying the MAPT-N279K mutation, which were related to oxidative stress, oxidative phosphorylation and neuroinflammation with an upregulation of the inflammation-associated protein osteopontin (OPN). Human FTD neurons survived less and elicited an increased microglial response after transplantation into the mouse forebrain, that we further characterized by single nucleus RNA-sequencing of microdissected grafts. Notably, downregulation of OPN in engrafted FTD neurons resulted in improved engraftment and reduced microglial infiltration, indicating an immune-modulatory role of OPN in patient neurons, which may represent a potential therapeutic target in FTD.
Published in
Osteopontin drives neuroinflammation and cell loss in MAPT-N279K frontotemporal dementia patient neurons
Al-Dalahmah O, Lam M, McInvale JJ et al. · Cell stem cell 2024 · PMID 38626772 · doi:10.1016/j.stem.2024.03.013
This dataset
Open GSE230450 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 GSE230450_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA961152 and SRA study SRP434253. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38626772) ↗
Study design
6 conditions, mostly with about 4 replicates each
iPSC neurons, CtrlSPP1 ×4 iPSC neurons, CtrlGFP ×4 iPSC neurons, FTDshSPP1 ×4 iPSC neurons, FTDsc ×4 iPSC neurons, FTDvehicle ×3 iPSC neurons, FTDmetformin ×3

Supports a between-group comparison across 22 samples.

How we read this: 6 replicated groups read from 22 sample titles; they account for 22 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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