Single cell RNA-seq from Trim28 ovary knockout and wildtype mice ovaries and testis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA700981 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13666806.fastq.gz | Fastqsanger.gz | |||
| SRR13666807.fastq.gz | Fastqsanger.gz | |||
| SRR13666808.fastq.gz | Fastqsanger.gz | |||
| SRR13666809.fastq.gz | Fastqsanger.gz | |||
| SRR13666810.fastq.gz | Fastqsanger.gz |
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Project description:Single cell RNA-seq (scRNA-seq) from Trim28 ovary knockout and wildtype mice ovaries and testis to help elucidate the function of Trim28 in the adult mouse ovaries. The analysis revealed that loss of Trim28 in the adult mouse ovaries lead to a transcriptional repogramming of the Granulosa cells towards the Sertoli cell fate. Therefore, Trim28 has a function to maintain the adult ovarian cell identity
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Project description:We study the role of the protein Trim28 in the maintenance of sexual identity of the adult ovary. With the help of conditional knock out (cKO) of Trim28 using the Nr5a1:Cre, we observed that deletion of the Trim28 gene in granulosa cells of the adult ovary induces their transdifferentiation into Sertoli cells, the supporting cell lineage of the testicular seminiferous tubules. FOXL2 expression has disappeared and follicles were completely remodeled into tubular structures with cells that expressed the Sertoli cell markers SOX8, SOX9 and DMRT1. Histological analysis confirmed the progressive reorganization of ovarian follicles into tubular structures and the and the transdifferentiation of granulosa cells by cells with a Sertoli cell morphology. TRIM28 acts as a SUMO-E3 ligase by interacting with the SUMO-E2 conjugating enzyme UBC9 (encoded by the Ube2i gene) via the Plant homeodomain (PHD), and can self-SUMOylate. To study in vivo the role of TRIM28-dependent SUMOylation, we generated a point mutation in exon 13 of mouse Trim28 within the PHD domain of the TRIM28 protein (C651F) that abrogates its SUMO-E3 ligase activity. We generated Trim28Phd/cKO mice (termed PHD mutant). Like in cKO ovaries, FOXL2 expression was undetectable, whereas we observed expression of the Sertoli cell markers SOX9, SOX8 and DMRT1 within structures organized in pseudo-tubules in PHD ovaries. Our results indicate that maintenance of the female pathway in the adult ovary depends on the E3-SUMO ligase activity of TRIM28.
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