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Genetic variation in the anaphase promoting complex modulates fertility and chromosome alignment defects in the absence of KIF18A

GSE281149 Mus musculus (mouse) RNA-seq (gene expression) 60 samples Submitted 2024/12/02 Platform GPL21103
At a glance

RNA-seq (gene expression) · mouse · 60 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
Mus musculus (mouse)
Samples
60 samples: 29 conditions, mostly in duplicateGroups 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.
Summary (written by the submitters)
The kinesin family member 18A (Kif18a) is an essential regulator of microtubule dynamics and chromosome alignment during mitosis. Laboratory mice with a loss of function mutation in Kif18a are are infertile due to mitotic arrest of germ cells, but this phenotype shows variable penetrance depending on genetic background. Kif18a is also necessary for mitotic progression of chromosomally unstable cancer cells, which exhibit mitotic arrest in the absence of KIF18A function.
Read the full summary ↓
While it is clear that functional dependency on KIF18A varies by cell type and genetic context, the heritable factors that influence this dependency remain unknown. To address this, we took advantage of the variable penetrance observed in different mouse strain backgrounds to screen for genetic loci that modulate germ cell depletion in the absence of KIF18A. We found a significant association between the severity of germ cell depletion and a locus on Chr5 wherein anaphase promoting complex subunits 5 (Anapc5) and 7 (Anapc7) were the top candidate genes. We compared the expression of both genes at key timepoints in gondal development and found that both genes were differentially expressed in sensitive strain backgrounds when compared to resistant strain backgrounds. We also identify a novel retroviral insertion in Anapc7 that may in part explain the observed expression differences. In cell line models, we found that depletion of KIF18A induced mitotic arrest, which was partially rescued by co-depletion of APC7 and exacerbated by co-depletion of APC5. These findings suggest that differential expression and activity of Anapc5 and Anapc7 may influence sensitivity to KIF18A depletion in germ cells and CIN cells, with potential implications for optimizing antineoplastic therapies.
This dataset
Open GSE281149 in finder → Find more mouse 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 GSE281149_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 PRJNA1182387 and SRA study SRP543348. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
29 conditions, mostly in duplicate
ovary_B6_1 ×2 ovary_B6_2 ×2 ovary_B6_3 ×2 testis_B6_1 ×2 testis_B6_2 ×2 testis_B6_3 ×2 testis_B6_4 ×2 testis_B6_5 ×2 +23 more

Supports a between-group comparison across 58 samples.

How we read this: 29 replicated groups read from 60 sample titles; they account for 58 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

+ 20 more — browse all 60 samples with per-sample file links →

Datasets on a similar topic

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