Sex differences orchestrated by androgens at single-cell resolution

• 成果类型: Article
• 署名作者: Li, Fei; Xing, Xudong; Jin, Qiqi; Wang, Xiang-Ming; Dai, Pengfei; Han, Ming; Shi, Huili; Zhang, Ze; Shao, Xianlong; Peng, Yunyi; Zhu, Yiqin; Xu, Jiayi; Li, Dan; Chen, Yu; Wu, Wei; Wang, Qiao; Yu, Chen; Chen, Luonan; Bai, Fan; Gao, Dong
• 署名单位: Chinese Academy of Sciences; Center for Excellence in Molecular Cell Science, CAS; Peking University; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; ShanghaiTech University; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Shanghai Normal University; Memorial Sloan Kettering Cancer Center; Fudan University; Shenzhen Bay Laboratory
• 刊物名称: Nature
• ISSN/ISSBN: 0028-4849
• DOI: 10.1038/s41586-024-07291-6
• 发表日期: 2024-05-02
• 关键词: cd8(+) t-cells; innate lymphoid-cells; prostate-cancer; memory; foxo1; expression; differentiation; immunotherapy; maintenance; inhibitors

摘要

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. The effects of sex and androgens on the molecular programs and cellular populations are explored using a single-cell transcriptomic atlas comprising over 2.3 million cells from different tissues in Mus musculus.