Cell-fate transition and determination analysis of mouse male germ cells throughout development

Jiexiang Zhao, Ping Lu, Cong Wan, Yaping Huang, Manman Cui, Xinyan Yang, Yuqiong Hu, Yi Zheng, Ji Dong, Mei Wang, Shu Zhang, Zhaoting Liu, Shuhui Bian, Xiaoman Wang, Rui Wang, Shaofang Ren, Dazhuang Wang, Zhaokai Yao, Gang Chang (), Fuchou Tang () and Xiao-Yang Zhao ()
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Jiexiang Zhao: State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University
Ping Lu: Beijing Advanced Innovation Center for Genomics (ICG), School of Life Sciences, Peking University
Cong Wan: State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University
Yaping Huang: State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University
Manman Cui: State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University
Xinyan Yang: State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University
Yuqiong Hu: Beijing Advanced Innovation Center for Genomics (ICG), School of Life Sciences, Peking University
Yi Zheng: State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University
Ji Dong: Beijing Advanced Innovation Center for Genomics (ICG), School of Life Sciences, Peking University
Mei Wang: State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University
Shu Zhang: Beijing Advanced Innovation Center for Genomics (ICG), School of Life Sciences, Peking University
Zhaoting Liu: State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University
Shuhui Bian: Beijing Advanced Innovation Center for Genomics (ICG), School of Life Sciences, Peking University
Xiaoman Wang: State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University
Rui Wang: Beijing Advanced Innovation Center for Genomics (ICG), School of Life Sciences, Peking University
Shaofang Ren: State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University
Dazhuang Wang: State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University
Zhaokai Yao: State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University
Gang Chang: Shenzhen University Health Science Center
Fuchou Tang: Beijing Advanced Innovation Center for Genomics (ICG), School of Life Sciences, Peking University
Xiao-Yang Zhao: State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University

Nature Communications, 2021, vol. 12, issue 1, 1-20

Abstract: Abstract Mammalian male germ cell development is a stepwise cell-fate transition process; however, the full-term developmental profile of male germ cells remains undefined. Here, by interrogating the high-precision transcriptome atlas of 11,598 cells covering 28 critical time-points, we demonstrate that cell-fate transition from mitotic to post-mitotic primordial germ cells is accompanied by transcriptome-scale reconfiguration and a transitional cell state. Notch signaling pathway is essential for initiating mitotic arrest and the maintenance of male germ cells’ identities. Ablation of HELQ induces developmental arrest and abnormal transcriptome reprogramming of male germ cells, indicating the importance of cell cycle regulation for proper cell-fate transition. Finally, systematic human-mouse comparison reveals potential regulators whose deficiency contributed to human male infertility via mitotic arrest regulation. Collectively, our study provides an accurate and comprehensive transcriptome atlas of the male germline cycle and allows for an in-depth understanding of the cell-fate transition and determination underlying male germ cell development.

Date: 2021
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DOI: 10.1038/s41467-021-27172-0

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