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Astrocyte-derived cholesterol drives synaptic gene expression in developing neurons and reciprocal astrocytic transcriptional programs

GSE289420 Homo sapiens (human) RNA-seq (gene expression) 416 samples Submitted 2026/07/28 Platform GPL24247Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 416 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
416 samples: 416 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)
Astrocytes participate in neuronal synaptic programs enriched for genetic associations in schizophrenia and autism spectrum disorders (ASD). To understand how these co-regulated cellular programs are induced during early neuronal development, we studied astrocytes and iPSC-derived neurons in co-cultures and mono-cultures across 16 time points spanning 0.5 hours to 8 days.
Read the full summary ↓
We found that upregulation of astrocytic cholesterol biosynthesis genes preceded the activation of synaptic gene programs in neurons and upregulation of astrocytic Nrxn1. Neuronal knockdown of key cholesterol receptors led to downregulation of neuronal synaptic genes and induced a robust transcriptional response in astrocytes, including further upregulation of Nrxn1. This suggests that astrocyte-supplied cholesterol drives neuronal synaptic changes and that bi-directional signalling is occurring. The upregulated neuronal genes were enriched for deleterious variants associated with schizophrenia and neurodevelopmental disorders, suggesting that their pathogenic effect may be, in part, mediated by reduced neuronal buffering capacity against fluctuations in astrocyte-derived cholesterol supply. These findings highlight the critical role of astrocyte-neuron interactions in psychiatric and neurodevelopmental disorders, particularly in relation to lipid metabolism and synaptic plasticity.
This dataset
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.

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 GSE289420_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1222887 and SRA study SRP563483. Searching any of these in the dataset finder brings you back here.

Study design
416 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 the first 400 of 416 sample titles: 400 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

+ 376 more — browse all 416 samples with per-sample file links →

Datasets on a similar topic

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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.