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Publication : RNA helicase DDX5 acts as a critical regulator for survival of neonatal mouse gonocytes.

First Author  Xia Q Year  2021
Journal  Cell Prolif Volume  54
Issue  5 Pages  e13000
PubMed ID  33666296 Mgi Jnum  J:306880
Mgi Id  MGI:6718045 Doi  10.1111/cpr.13000
Citation  Xia Q, et al. (2021) RNA helicase DDX5 acts as a critical regulator for survival of neonatal mouse gonocytes. Cell Prolif 54(5):e13000
abstractText  OBJECTIVES: Mammalian spermatogenesis is a biological process of male gamete formation. Gonocytes are the only precursors of spermatogonial stem cells (SSCs) which develop into mature spermatozoa. DDX5 is one of DEAD-box RNA helicases and expresses in male germ cells, suggesting that Ddx5 plays important functions during spermatogenesis. Here, we explore the functions of Ddx5 in regulating the specification of gonocytes. MATERIALS AND METHODS: Germ cell-specific Ddx5 knockout (Ddx5(-/-) ) mice were generated. The morphology of testes and epididymides and fertility in both wild-type and Ddx5(-/-) mice were analysed. Single-cell RNA sequencing (scRNA-seq) was used to profile the transcriptome in testes from wild-type and Ddx5(-/-) mice at postnatal day (P) 2. Dysregulated genes were validated by single-cell qRT-PCR and immunofluorescent staining. RESULTS: In male mice, Ddx5 was expressed in germ cells at different stages of development. Germ cell-specific Ddx5 knockout adult male mice were sterile due to completely devoid of germ cells. Male germ cells gradually disappeared in Ddx5(-/-) mice from E18.5 to P6. Single-cell transcriptome analysis showed that genes involved in cell cycle and glial cell line-derived neurotrophic factor (GDNF) pathway were significantly decreased in Ddx5-deficient gonocytes. Notably, Ddx5 ablation impeded the proliferation of gonocytes. CONCLUSIONS: Our study reveals the critical roles of Ddx5 in fate determination of gonocytes, offering a novel insight into the pathogenesis of male sterility.
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