| Description |
Evolutionarily and historically, sex is a fundamental biological characteristic that, to some degree, influences nearly all human phenotypes, thus, leading to sex differences prevalently seen in human physiology and disease. However, until recently, the comprehensive molecular and cellular profiles of sex differences, as well as the roles of androgen, one of postulated chief factors contributing to sex differences, are still lack. Here, we constructed a high-dimensional single-cell transcriptomic landscape involving both sex and androgen perturbation throughout 17 tissues in the whole organism of mouse. We systematically dissected cross-tissue effects of sex, androgen and the interaction between the two in terms of molecular programs, transcriptional regulation networks, cellular communications and immune ecosystem. In particular, we observed immune compartments that differed between sexes were concordantly modulated by androgen across multiple tissues. Additionally, we systematically elucidated the effects of sex and androgen in asthma induced by IL33, as well as myocarditis induced by COVID19 mRNA vaccine. Our work provides a comprehensive cross-tissue transcriptomic atlas involving sex and androgen, uncovers targeting androgen modulates sex-biased immune ecosystem, and establishes a cellular and molecular roadmap for elucidating the mechanisms, as well as identifying therapeutic targets for sex-biased human traits including but not limited to disease. |
