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The disease modeling of Jacob Syndrome reveals an aberrant genome-wide expression modulation from the Y chromosome [RNA-seq]

GSE264395 Homo sapiens (human) RNA-seq (gene expression) 99 samples Submitted 2025/04/28 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 99 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
99 samples
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
An iPSC-based model of 47,XYY Jacobs syndrome reveals a DNA methylation-independent transcriptional dysregulation shared with male X aneuploid cellsGenome research · 2025
Summary (written by the submitters)
Male sex chromosome aneuploidies are frequent genetic aberrations in humans characterized by additional X or Y complements in the contest of a 46,XY karyotype. Among male aneuploidies, Klinefelter (KS) and Jacob Syndromes (JS), carrying 47,XXY and 47,XYY chromosomes, respectively, share several clinical features, including sterility, hormonal deficits, neurocognitive delay, and skeletal-muscle defects.
Read the full summary ↓
In this study, we generated and characterized the inaugural cohort of 47,XYY human induced pluripotent stem cells (iPSCs). We profiled the transcriptome of fibroblasts, iPSCs, and iPSCs-derived neural stem cells (NSCs) to investigate the transcriptional consequences of Y chromosome overdosage across three different cell types. Our data defined subsets of genes sensitive to Y dosage that includes i) non-PAR Y-linked (NPY) genes shared among cell types, ii) genes residing on the X and Y pseudo-autosomal region 1 (PAR1), and iii) autosomal genes that display a mild degree of tissue-specificity. By comparing the expression and identity of PAR1 in KS and JS-derived cells, we confirmed their obligate dosage sensitivity to sex chromosome numbers in a cell type-dependent fashion, and we proved that PAR1 genes are differentially expressed from X and Y chromosomes. We also defined a shared transcriptional signature in X and Y aneuploidies, by comparing sex and autosomal dysregulated genes, that could explain the shared clinical manifestations in JS and KS patients. Furthermore, we demonstrated a regulatory function of NPY genes on their non-PAR homologs on the X chromosome (NPX). By mechanistically linking the expression of X and Y gene pairs, we revealed that NPY genes in overdosage negatively modulate in trans the transcription of their NPX homologs. Finally, we assessed the genome-wide methylation status in cells carrying Y aneuploidies and defined that the additional Y chromosome does not dramatically alter the global DNA methylation status. Our findings expand the knowledge on X and Y chromosome cross-modulation and impact on human gene expression, and suggest that disease modeling of sex aneuploidy through iPSCs may provide an ideal platform for understanding the global effects of aneuploidies in disease-relevant cell types.
Published in
An iPSC-based model of 47,XYY Jacobs syndrome reveals a DNA methylation-independent transcriptional dysregulation shared with male X aneuploid cells
Astro V, Cardona-Londoño KY, Cortés-Medina LV et al. · Genome research 2025 · PMID 40494628 · doi:10.1101/gr.279716.124
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 GSE264395_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 PRJNA1102336 and SRA study SRP502835. Searching any of these in the dataset finder brings you back here.

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