ESPEYB21 14. The Year in Science and Medicine Steroid Hormones from Basics to Clinic (1 abstracts)
14.9. 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 & Dong Gao
Nature 629, 193–200 (2024). doi: 10.1038/s41586-024-07291-6
Brief Summary:This study assembled a single-cell transcriptomic atlas representing over 2.3 million cells from 17 tissues in mice. Investigations of the scRNA-seq data focussed on effects of sex and androgens on the molecular programs and cellular populations in female and male mice as well as male androgen-deprived, and female androgen-treated mice. Data were then used to gain novel molecular insight into sex-related human disorders as available in the UK Biobank study.
Transcript data quantify the active (expressed) genes in a cell, thereby offering insights into cellular function and regulation. Therefore, this new atlas of single-cell transcriptomics data created from many different tissues in mice serves as a rich resource (library) for research questions in mice and beyond. The authors claim that this single-cell atlas may identify cellular targets for sex-biased diseases (e.g. especially those dependent on androgen action) based on the expression patterns of risk genes. They demonstrate this point using human ICD coded disease and genotype data from the UK Biobank study.
The study design - to produce scRNA-seq data, not only in healthy male and female mice, but also in androgen-deprived males and androgen treated-females – enabled novel insights into the role of androgens in sex differences. As sex differences are seen in many and diverse mammalian complex traits, a systemic approach was taken including cells of many different organs. The main finding was that the effect of androgens was positively correlated with sex differences in tissue cell composition. Additionally, known sex differences in the immune system and response were confirmed and an essential role was found for MHC genes in sex differences of human diseases. Some of the observed sex-specific effects could be modulated by targeting the androgen pathway.
Helpfully, the authors developed a web tool to allow customized visualization of their data and a computational pipeline to explore the primary and secondary effects of the androgen–androgen receptor (https://casadbtools.com/andr_effect).
Volume 21
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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