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| Status |
Public on Jan 22, 2025 |
| Title |
Chromosome X Dosage Modulates Development of Aneuploidy in Genetically Diverse Mouse Embryonic Stem Cells [D0_scRNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The genetic integrity of pluripotent stem cells (PSC) is integral to their applications in research and therapy, but it is compromised by frequent development of copy number variations. Little is known about the basis of the variable genomic integrity among different PSC lines. Here we identify aneuploidies using RNA-seq and proteomics data from a panel of mouse embryonic stem cell (mESC) lines derived from 170 Diversity Outbred mice. We identified 62 lines with detectable aneuploid subpopulations and a subset of originally XX lines that lost one Chromosome X (XO). Strikingly, a much lower proportion of XX lines were aneuploid, compared to XY or XO lines. Two single-cell RNA-seq data sets demonstrated that aneuploid XY DO mESC also show lower Chromosome X gene expression and that XY mESC accumulate higher aneuploid proportions in culture than isogenic XX lines. Possible mechanisms for this protective effect of X chromosome dosage include our discovery that the lines with two active X Chromosomes have a higher expression of 2-cell-like state genes, and differential expression of X-linked tumor suppressor genes associated with DNA damage response.
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| Overall design |
The sample submitted contains embryonic stem cells (ESCs) derived from diversity outbred (DO) mice. The cell lines were derived indepdently and pooled in equal proportion for sequencing. The pooled sample was then divided and sequenced across 4 lanes.
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| Web link |
https://www.biorxiv.org/content/10.1101/2024.06.29.601344v1
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| Contributor(s) |
Stanton A, Aydin S, Skelly D, Stavish D, Leonhard K, Taapken S, McIntire E, Pankratz M, Czechanski A, Ludwig T, Choi T, Gygi S, Barbaric I, Munger S, Reinholdt L, Pera M |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Jan 21, 2025 |
| Last update date |
Jan 24, 2025 |
| Contact name |
Selcan Aydin |
| Organization name |
The Jackson Laboratory
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| Street address |
600 Main Street
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| City |
Bar Harbor |
| State/province |
Maine |
| ZIP/Postal code |
04609 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (1) |
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| Relations |
| BioProject |
PRJNA1213835 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE287621_RAW.tar |
61.6 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
| GSE287621_strain_barcodes.tar.gz |
30.9 Kb |
(ftp)(http) |
TAR |
SRA Run Selector |
| Raw data are available in SRA |
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