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Developmental convergence and divergence in human stem cell models of autism spectrum disorder

GSE271853 Homo sapiens (human) RNA-seq (gene expression) 476 samples Submitted 2025/11/12 Platform GPL20301Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 476 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
476 samples: 5 conditions, mostly with about 112 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
Developmental convergence and divergence in human stem cell models of autismNature · 2026
Summary (written by the submitters)
Two decades of genetic studies in autism spectrum disorder (ASD) have identified over a hundred genes harboring rare risk mutations. Despite this substantial heterogeneity, transcriptomic and epigenetic analyses have identified convergent patterns of dysregulation across ASD post-mortem brain. To identify shared and distinct mechanisms of ASD-linked mutations, we assembled the largest patient hiPS cell cohort to date, consisting of 70 hiPS cell lines after stringent quality control representing 8 ASD-associated mutations, idiopathic ASD, and 20 lines from non-affected controls.
Read the full summary ↓
We used these hiPS lines to generate human cortical organoids (hCO), profiling by RNAseq at four distinct timepoints up to 100 days after in vitro differentiation. Early timepoints harbored the largest mutation-specific changes, but different mutations converged on shared transcriptional changes as development progressed. We identified a shared RNA and protein interaction network, which was enriched in ASD risk genes and predicted to drive the observed down-stream changes in gene expression. CRISPR-Cas9 screening of these candidate transcriptional regulators in induced human neural progenitors validated their downstream molecular convergent effects. These data illustrate how genetic risk can propagate via transcriptional regulation to impact convergently dysregulated pathways, providing new insight into the convergent impact of ASD genetic risk on human neurodevelopment.
Published in
Developmental convergence and divergence in human stem cell models of autism
Gordon A, Yoon SJ, Bicks LK et al. · Nature 2026 · PMID 41611887 · doi:10.1038/s41586-025-10047-5
This dataset
Open GSE271853 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 GSE271853_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 PRJNA1133757 and SRA study SRP648830. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41611887) ↗
Study design
5 conditions, mostly with about 112 replicates each
FF3 ×112 FF5 ×96 FF4 ×59 FF2 ×53 Dup ×13 Pool-1-ATCACGAT ×1 Pool-3-CCGTCCCG ×1 Pool-4-ACAGTGAT ×1 +64 more

Supports a between-group comparison across 333 samples.

How we read this: 5 replicated groups read from the first 400 of 476 sample titles; they account for 333 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

+ 436 more — browse all 476 samples with per-sample file links →

Datasets on a similar topic

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