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Schizophrenia risk gene ZNF536 modulates retinoic acid response and neuronal gene networks in SH-SY5Y cells

GSE304368 Homo sapiens (human) RNA-seq (gene expression) 18 samples Submitted 2025/09/30 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 18 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
18 samples: 6 conditions, mostly in triplicateGroups 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
Schizophrenia risk gene ZNF536 modulates retinoic acid response and neuronal gene networks in SH-SY5Y cellsFrontiers in molecular neuroscience · 2025
Summary (written by the submitters)
ZNF536, a brain-specific transcriptional repressor, has recently emerged as a candidate risk gene for schizophrenia (SZ), yet its functional role in human neurodevelopment remains poorly understood. In this study, we used CRISPR/Cas9 genome editing to generate a dual-allelic ZNF536 knockout model in SH-SY5Y cells, combining a 103 kb deletion encompassing SZ-associated intronic regions with a disruption of zinc finger domains in exon 2.
Read the full summary ↓
Transcriptome profiling of mutant cells undergoing all-trans retinoic acid (ATRA)-induced differentiation revealed impaired activation of retinoic acid receptor (RAR) target genes, reduced neurite outgrowth, and failure of neuronal maturation. Notably, gene set enrichment analysis uncovered dysregulation of E2F4-mediated cell cycle pathways, suggesting that ZNF536 modulates neurogenic commitment through coordinated control of transcriptional repression and cell proliferation. Moreover, the targeted intronic deletion altered the expression of multiple SZ-associated genes, supporting the functional importance of cis-regulatory elements within ZNF536. Together, our results identify ZNF536 as a critical regulator of RA-responsive gene networks and neuronal differentiation, offering new mechanistic insights into its contribution to schizophrenia (SZ) pathogenesis.
Published in
Schizophrenia risk gene ZNF536 modulates retinoic acid response and neuronal gene networks in SH-SY5Y cells
Kurishev AO, Abashkin DA, Karpov DS et al. · Frontiers in molecular neuroscience 2025 · PMID 41163642 · doi:10.3389/fnmol.2025.1671354
This dataset
Open GSE304368 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 GSE304368_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 PRJNA1301126 and SRA study SRP606253. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41163642) ↗
Study design
6 conditions, mostly in triplicate
SH-SY5Y NTC basal ×3 SH-SY5Y KI/KI basal ×3 SH-SY5Y KI/del basal ×3 SH-SY5Y NTC RA treatment, Day7 ×3 SH-SY5Y KI/KI RA treatment, Day7 ×3 SH-SY5Y KI/del RA treatment, Day7 ×3

Supports a between-group comparison across 18 samples.

How we read this: 6 replicated groups read from 18 sample titles; they account for 18 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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