Single-cell RNA-seq uncovers dynamic processes orchestrated by RNA-binding protein DDX43 in chromatin remodeling during spermiogenesis

作者全名："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"

作者地址："[Tan, Huanhuan; Zhou, Congjin; Wang, Yanfeng; Zhang, Shu; Yang, Pinglan; Guo, Rui; Zhang, Jinwen; Ye, Lan; Cui, Yiqiang; Zheng, Ke] Nanjing Med Univ, State Key Lab Reprod Med, Nanjing 211166, Peoples R China; [Wang, Weixu; Chen, Wei; Ni, Ting] Fudan Univ, Sch Life Sci,Human Phenome Inst, Shanghai Engn Res Ctr Ind Microorganisms, State Key Lab Genet Engn,Collaborat Innovat Ctr G, Shanghai 200438, Peoples R China; [Wang, Weixu; Chen, Wei; Ni, Ting] Fudan Univ, Huashan Hosp, Shanghai 200438, Peoples R China; [Tan, Huanhuan] Chongqing Med Univ, Affiliated Hosp 1, Reprod Med Ctr, 1 Youyi Rd, Chongqing 400016, Peoples R China; [Wang, Weixu] Helmholtz Ctr Munich, Inst Computat Biol, Munich, Germany"

通信作者："Cui, YQ; Zheng, K (通讯作者)，Nanjing Med Univ, State Key Lab Reprod Med, Nanjing 211166, Peoples R China.; Ni, T (通讯作者)，Fudan Univ, Sch Life Sci,Human Phenome Inst, Shanghai Engn Res Ctr Ind Microorganisms, State Key Lab Genet Engn,Collaborat Innovat Ctr G, Shanghai 200438, Peoples R China.; Ni, T (通讯作者)，Fudan Univ, Huashan Hosp, Shanghai 200438, Peoples R China."

来源：NATURE COMMUNICATIONS

ESI学科分类：　

WOS号：WOS:001026269800001

JCR分区：Q1

影响因子：16.6

年份：2023

卷号：14

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："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."

基金机构："National Key Research and Development Program of China [2022YFC2703501, 2021YFC2700200, 2018YFC1003500]; National Natural Science Foundation of China [31970791, 92249302, 32170858]; Excellent Youth Foundation of Jiangsu Scientific Committee [BK20211532]"

基金资助正文："The authors thank Prof. Zheng Sun (Baylor College of Medicine, USA) for critical reading of the manuscript, thank Fangfang Li (Nanjing Medical University, China) for providing technical assistance with RG4 EMSA, and thank Huiling Li (Nanjing Medical University, China) for help with manuscript preparation. This work was supported by the National Key Research and Development Program of China [2022YFC2703501, 2021YFC2700200, 2018YFC1003500]; National Natural Science Foundation of China [31970791, 92249302, 32170858]; Excellent Youth Foundation of Jiangsu Scientific Committee [BK20211532]."