Open AccessRNA helicase DDX5 acts as a critical regulator for survival of neonatal mouse gonocytes
Author(s) -
Xia Qing,
Cui Guizhong,
Fan Ye,
Wang Xiuqin,
Hu Gongcheng,
Wang Lisha,
Luo Xi,
Yang Lele,
Cai Qingqing,
Xu Kaibiao,
Guo Wenjing,
Gao Minghui,
Li Yingying,
Wu Ji,
Li Wei,
Chen Jiayu,
Qi Huayu,
Peng Guangdun,
Yao Hongjie
Publication year - 2021
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.13000
Subject(s) - gonocyte , biology , germ cell , microbiology and biotechnology , rna helicase a , transcriptome , germline , genetics , rna , gene , gene expression , helicase
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.