GEO series

Histone H1 Variants Regulate Neurodevelopmental Transcriptional Programs in Autism and Schizophrenia with 16p11.2 CNV

GSE292323 Homo sapiens (human) RNA-seq (gene expression) 14 samples Submitted 2025/05/25 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 14 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: 14 samples: 4 × SH-SY5Y, WT vs 2 × SH-SY5Y, H1.2 OE vs 2 × SH-SY5Y, H1.5 OE vs 2 × SH-SY5Y, H1.2 OE + H1.5 OEGroups 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)

Neurodevelopmental disorders, including autism spectrum disorder (ASD) and schizophrenia (SCZ), involve widespread transcriptional dysregulation. Copy number variations (CNVs) at 16p11.2 are among the strongest genetic risk factors for ASD and SCZ, yet the molecular mechanisms by which these CNV contribute to neurodevelopmental pathology remain unclear.

Read the full summary ↓

Here, we identify significant genetic associations between ASD susceptibility and the HIST1 histone gene cluster through genome-wide analysis. Transcriptomic profiling across multiple experimental systems—including postmortem human brain tissue, patient-derived neural progenitor cells (NPCs), neurons, and cerebral organoids—reveals consistently elevated expression of histone variants H1.2 and H1.5 in idiopathic ASD and in 16p11.2 CNV carriers with ASD or SCZ, but not in idiopathic SCZ or bipolar disorder. Functional assays demonstrate that dysregulated H1 expression disrupts networks involved in synaptic signalling, chromatin remodelling, and neural differentiation. Using a deep learning framework incorporating Variational Autoencoder (VAE) and SHAP-based feature importance, we uncover distinct regulatory pathways driven by H1 overexpression. Notably, this overexpression induces bidirectional transcriptional changes within the 16p11.2 locus, mirroring expression signatures of both deletions and duplications. Our findings establish H1.2 and H1.5 as key regulators of transcriptional programs in neurodevelopmental disorders, highlighting chromatin-mediated mechanisms underlying ASD and SCZ and their potential as biomarkers.

This dataset

Open GSE292323 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 GSE292323_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 PRJNA1237906 and SRA study SRP571420. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42169156) ↗

Study design

4 × SH-SY5Y, WT vs 2 × SH-SY5Y, H1.2 OE vs 2 × SH-SY5Y, H1.5 OE vs 2 × SH-SY5Y, H1.2 OE + H1.5 OE

Supports a between-group comparison across 10 samples.

How we read this: 4 replicated groups read from 14 sample titles; they account for 10 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

GSM8856310 SH-SY5Y, WT SH-SY5Y, WT
GSM8856311 SH-SY5Y, WT_rep2 SH-SY5Y, WT
GSM8856312 SH-SY5Y, WT_rep3 SH-SY5Y, WT
GSM8856313 SH-SY5Y, WT_rep4 SH-SY5Y, WT
GSM8856314 SH-SY5Y, H1.2 OE SH-SY5Y, H1.2 OE
GSM8856315 SH-SY5Y, H1.2 OE_rep2 SH-SY5Y, H1.2 OE
GSM8856316 SH-SY5Y, H1.5 OE SH-SY5Y, H1.5 OE
GSM8856317 SH-SY5Y, H1.5 OE_rep2 SH-SY5Y, H1.5 OE
GSM8856318 SH-SY5Y, H1.2 OE + H1.5 OE SH-SY5Y, H1.2 OE + H1.5…
GSM8856319 SH-SY5Y, H1.2 OE + H1.5 OE_rep2 SH-SY5Y, H1.2 OE + H1.5…
GSM8856320 SH-SY5Y, WT_Si
GSM8856321 SH-SY5Y, H1.2 Si
GSM8856322 SH-SY5Y, H1.5 Si
GSM8856323 SH-SY5Y, H1.2 Si + H1.5 Si

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