Experiment Id | GSE141190 | Name | EXOSC10 sculpts the transcriptome during oocyte growth-to-maturation transition |
Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
Source | GEO | Curation Date | 2025-01-08 |
description | Growing mammalian oocytes accumulate substantial amounts of RNA, most of which are degraded during the subsequent maturation stage. The growth-to-maturation transition begins with germinal vesicle breakdown (GVBD, envisioned as nuclear envelope breakdown) and is critical for oocyte quality. However, the concomitant changes in the transcriptome during GVBD as well as the underlying machinery remained unclear. Here, we report that an RNA exosome-associated RNase, EXOSC10, sculpts the transcriptome at multiple level to facilitate the oocyte growth-to-maturation transition. We establish an oocyte-specific knockout of Exosc10 in mice using CRISPR/Cas9 and find female subfertility due to failed GVBD. By performing single oocyte RNA-seq in different ways, we document dysregulated transcriptomes, unsuccessfully processed rRNAs in mutant oocytes, and many up-regulated RNAs that encode proteins important for endomembrane trafficking, meiotic cell cycle and RNA metabolism. EXOSC10-depleted oocytes have impaired endomembrane components including endosome, lysosome, ER and Golgi. In addition, CDK1 fails to be activated possibly due to persistent WEE1 activity, which blocked lamina phosphorylation and disassembly in mutant oocytes. Collectively, we propose that EXOSC10 promotes the growth-to-maturation transition in mouse oocytes by degrading mRNAs that encode growth-phase factors and sculpting the transcriptome to support the maturation phase of oogenesis. There are 64 single oocyte polyA-RNA libraries generated with poly(A)-based enrichment and reverse transcription, including 22 at GV stage, 19 at GV+3hr stage, and 23 at MII stage. In addition, there are 22 single single oocyte RiboMinus libraries generated independent of poly(A), including 15 at GV stage and 7 at MII stage. Morever, there are 22 single oocyte rRNA libraries generated by total RNA extraction without ribosome depletion. Each stage contains control oocytes and Exosc10 oocyte-specific knockout oocytes (cKO). The information of the stage, genotype, female ID and oocyte ID is in the name of each file: stage_genotype_femaleID_oocyteID. In each oocyte, equal amounts of ERCC spike-in mix was added. |