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Trisomy 21 drives ADARB1 overexpression and premature RNA recoding in the developing fetal brain

GSE301886 Homo sapiens (human) RNA-seq (gene expression) 94 samples Submitted 2026/04/08 Platform GPL21290
At a glance

RNA-seq (gene expression) · human · 94 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
94 samples: 54 × Control, vs 40 × T21,Groups 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
Trisomy 21 Drives ADARB1 Overexpression and Premature RNA Recoding in the Developing Fetal BrainNature communications · 2026
Summary (written by the submitters)
Understanding how chromosome 21 gene dosage contributes to neurodevelopmental and systemic phenotypes in trisomy 21 (T21) remains a fundamental challenge. We performed transcriptome-wide RNA sequencing on fetal cortical and hippocampal tissues from 20 T21 cases and 27 euploid controls collected between 13–22weeks post-conception—a critical period for human brain development.
Read the full summary ↓
Differential expression analysis revealed 572 dysregulated genes in the cortex and 519 in the hippocampus (FDR < 5%), with significant enrichment for chromosome 21 genes. Functional enrichment analyses highlighted disruptions in neurodevelopmental, synaptic, and immune-related pathways. Among the most strongly dysregulated genes was ADARB1, a chromosome 21–encoded RNA editing enzyme, whose overexpression in T21 fetal brain was associated with increased adenosine-to-inosine (A-to-I) editing, including key recoding events in GRIA2 (p.R764G), GRIA3 (p.R775G), and GRIK2 (p.Y571C, p.Q621R). A meta-analysis incorporating nine independent transcriptomic datasets spanning early embryonic and progenitor cell types validated robust chromosome 21 dosage effects, including consistent ADARB1 overexpression. Extending these findings, a meta-analysis of A-to-I editing across datasets revealed widespread over-editing at 3′UTRs and at GRIA3 (p.R775G), a site critical for AMPA receptor desensitization. Together, these results implicate dysregulated RNA editing—driven by ADARB1 overexpression—as a novel post-transcriptional mechanism contributing to fetal neuropathology in T21 and provide a framework for understanding the broader molecular consequences of chromosome 21 dosage sensitivity during brain development.
Published in
Trisomy 21 Drives ADARB1 Overexpression and Premature RNA Recoding in the Developing Fetal Brain
Breen MS, Yang A, Wang X et al. · Nature communications 2026 · PMID 41917044 · doi:10.1038/s41467-026-70217-5
This dataset
Open GSE301886 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 GSE301886_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 PRJNA1287689 and SRA study SRP599023. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41917044) ↗
Study design
54 × Control, vs 40 × T21,

Supports a between-group comparison across 94 samples.

How we read this: 2 replicated groups read from 94 sample titles; they account for 94 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

+ 54 more — browse all 94 samples with per-sample file links →

Datasets on a similar topic

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