Sex differences in mammalian complex traits are prevalent and are intimately associated with androgens. 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.

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 & Dong Gao

Sex differences orchestrated by androgens at single-cell resolution

Nature, Volume 629, pages193–200 (2024)

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