We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Single-cell RNA-seq uncovers dynamic processes orchestrated by RNA-binding protein DDX43 in chromatin remodeling during spermiogenesis.
- Authors
Tan, Huanhuan; Wang, Weixu; Zhou, Congjin; Wang, Yanfeng; Zhang, Shu; Yang, Pinglan; Guo, Rui; Chen, Wei; Zhang, Jinwen; Ye, Lan; Cui, Yiqiang; Ni, Ting; Zheng, Ke
- Abstract
Mammalian spermatogenesis shows prominent chromatin and transcriptomic switches in germ cells, but it is unclear how such dynamics are controlled. Here we identify RNA helicase DDX43 as an essential regulator of the chromatin remodeling process during spermiogenesis. Testis-specific Ddx43 knockout mice show male infertility with defective histone-to-protamine replacement and post-meiotic chromatin condensation defects. The loss of its ATP hydrolysis activity by a missense mutation replicates the infertility phenotype in global Ddx43 knockout mice. Single-cell RNA sequencing analyses of germ cells depleted of Ddx43 or expressing the Ddx43 ATPase-dead mutant reveals that DDX43 regulates dynamic RNA regulatory processes that underlie spermatid chromatin remodeling and differentiation. Transcriptomic profiling focusing on early-stage spermatids combined with enhanced crosslinking immunoprecipitation and sequencing further identifies Elfn2 as DDX43-targeted hub gene. These findings illustrate an essential role for DDX43 in spermiogenesis and highlight the single-cell-based strategy to dissect cell-state-specific regulation of male germline development. Germ cells undergo dramatic chromatin and transcriptomic changes during spermatogenesis, though how this is controlled is not well established. Here they show that RNA-binding protein DDX43 directs the spermatid differentiation trajectory and regulates chromatin remodeling in spermiogenesis, which is partially mediated by its target gene Elfn2.
- Subjects
RNA-binding proteins; CHROMATIN; RNA sequencing; DNA helicases; CHROMATIN-remodeling complexes; RNA helicase; GERM cells
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-38199-w