Sex differences orchestrated by androgens at single-cell resolution

Fei Li, Xudong Xing, Qiqi Jin, Xiang-Ming Wang, Pengfei Dai, Ming Han, Huili Shi, Ze Zhang, Xianlong Shao, Yunyi Peng, Yiqin Zhu, Jiayi Xu, Dan Li, Yu Chen, Wei Wu, Qiao Wang, Chen Yu (), Luonan Chen (), Fan Bai () and Dong Gao ()
Additional contact information
Fei Li: Chinese Academy of Sciences
Xudong Xing: Peking University
Qiqi Jin: Chinese Academy of Sciences
Xiang-Ming Wang: Peking University
Pengfei Dai: Chinese Academy of Sciences
Ming Han: Chinese Academy of Sciences
Huili Shi: Chinese Academy of Sciences
Ze Zhang: University of Chinese Academy of Sciences
Xianlong Shao: Chinese Academy of Sciences
Yunyi Peng: Chinese Academy of Sciences
Yiqin Zhu: Chinese Academy of Sciences
Jiayi Xu: Shanghai Normal University
Dan Li: Memorial Sloan Kettering Cancer Center
Yu Chen: Memorial Sloan Kettering Cancer Center
Wei Wu: Fudan University
Qiao Wang: Fudan University
Chen Yu: Shenzhen Bay Laboratory
Luonan Chen: Chinese Academy of Sciences
Fan Bai: Peking University
Dong Gao: Chinese Academy of Sciences

Nature, 2024, vol. 629, issue 8010, 193-200

Abstract: Abstract Sex differences in mammalian complex traits are prevalent and are intimately associated with androgens1–7. However, a molecular and cellular profile of sex differences and their modulation by androgens is still lacking. Here we constructed a high-dimensional single-cell transcriptomic atlas comprising over 2.3 million cells from 17 tissues in Mus musculus and explored the effects of sex and androgens on the molecular programs and cellular populations. In particular, we found that sex-biased immune gene expression and immune cell populations, such as group 2 innate lymphoid cells, were modulated by androgens. Integration with the UK Biobank dataset revealed potential cellular targets and risk gene enrichment in antigen presentation for sex-biased diseases. This study lays the groundwork for understanding the sex differences orchestrated by androgens and provides important evidence for targeting the androgen pathway as a broad therapeutic strategy for sex-biased diseases.

Date: 2024
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DOI: 10.1038/s41586-024-07291-6

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