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Divergent proteome tolerance against gain and loss of chromosome arms

GSE293644 Homo sapiens Other; Expression profiling by high throughput sequencing 21 samples Submitted 2026/03/25 Platform GPL16791Platform GPL34284Platform GPL30882
Summary
How aneuploid cells tolerate chromosome arm gains or losses remains an open question. Using an isogenic human lung cell model with either 3p loss or 3q gain, combined with quantitative mass spectrometry and isotopic labeling, we reveal distinct proteostasis mechanisms for gain- and loss-type aneuploidy. Surprisingly, while compensation for 3q gain is primarily driven by increased degradation of excess protein complex subunits, 3p loss is neither counteracted by global protein degradation nor selectively reduced degradation, but rather by relatively upregulated protein synthesis to maintain protein complex stoichiometry. Additionally, proteins encoded on 3p exhibit increased thermal stability in loss-type aneuploidy, potentially via their interactions with other proteins from euploid chromosomes. Together, our findings uncover distinct proteomic buffering strategies that enable cells to tolerate either excessive or deficient single-arm aneuploidy.
Published in
Divergent proteome tolerance against gain and loss of chromosome arms
Di Y, Li W, Castellano JJ et al. · Molecular cell 2025 · PMID 41270725 · doi:10.1016/j.molcel.2025.10.023
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Direct links to NCBI, no account and no request form: the whole study as GSE293644_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 21 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1245409 and SRA study SRP576110. Searching any of these in the dataset finder brings you back here.

Study design
7 conditions, mostly in triplicate
3p loss cell, mRNA, ×3 Chr3 WT cell, mRNA, ×3 3q gain cell, mRNA, ×3 3p loss cell, ribosome profiling, ×3 3p WT cell, ribosome profiling, ×3 8p loss cell, mRNA, ×3 8p WT cell, mRNA, ×3

Supports a between-group comparison across 21 samples.

7 replicated groups read from 21 sample titles; they account for 21 of them. Check it against the sample list below before relying on it.

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