Uncovering the Molecular and Cellular Basis of Sex Differences Regulated by Androgens through Single-Cell Transcriptomics

Konsep Inti

Sex differences in complex traits are prevalent and linked to androgens, but a comprehensive molecular and cellular profile of these differences and their androgen regulation is lacking.

Abstrak

The content presents a high-dimensional single-cell transcriptomic atlas of over 2.3 million cells from 17 tissues in mice, which was used to explore the effects of sex and androgens on molecular programs and cellular populations.
Key highlights:

Sex-biased immune gene expression and immune cell populations, such as group 2 innate lymphoid cells, were found to be modulated by androgens.
Integration with the UK Biobank dataset revealed potential cellular targets and risk gene enrichment in antigen presentation for sex-biased diseases.
The study provides a foundation for understanding the sex differences orchestrated by androgens and supports targeting the androgen pathway as a therapeutic strategy for sex-biased diseases.

Statistik

Over 2.3 million cells from 17 tissues in Mus musculus were profiled.

Kutipan

"Sex differences in mammalian complex traits are prevalent and are intimately associated with androgens1,2,3,4,5,6,7."
"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."

Wawasan Utama Disaring Dari

Sex differences orchestrated by androgens at single-cell resolution - Nature

by Fei Li,Xudon... pada www.nature.com 04-10-2024

https://www.nature.com/articles/s41586-024-07291-6

Pertanyaan yang Lebih Dalam

How do the sex-biased molecular and cellular profiles identified in this study vary across different tissues and developmental stages?

The study revealed sex differences in molecular and cellular profiles across various tissues and developmental stages in Mus musculus. These differences were found to be orchestrated by androgens, with immune gene expression and immune cell populations being particularly affected. For instance, group 2 innate lymphoid cells showed sex-biased expression patterns that were modulated by androgens. The variations in these profiles across tissues and developmental stages suggest a complex interplay between sex, androgens, and cellular functions. Understanding these nuances is crucial for unraveling the mechanisms underlying sex differences in complex traits and disease susceptibility.

What are the potential limitations of using mouse models to study sex differences in humans, and how can these be addressed?

While mouse models provide valuable insights into sex differences and the role of androgens, there are limitations when extrapolating findings to humans. One major limitation is the evolutionary divergence between mice and humans, leading to differences in genetic backgrounds and physiological responses. Additionally, the dosage and effects of androgens may vary between species. To address these limitations, researchers can consider using humanized mouse models that incorporate human genes or tissues. Furthermore, conducting comparative studies across species and validating findings in human cohorts can help bridge the translational gap and enhance the relevance of mouse model data to human biology.

What other hormonal or genetic factors, beyond androgens, might contribute to the observed sex differences in complex traits and disease susceptibility?

In addition to androgens, other hormonal and genetic factors may play a role in shaping sex differences in complex traits and disease susceptibility. Estrogens, progesterone, and other sex hormones are known to influence various physiological processes and immune responses, contributing to sex-specific outcomes. Genetic factors, such as sex chromosome genes and epigenetic modifications, can also impact gene expression and cellular functions differently in males and females. Understanding the intricate interactions between these factors and their combined effects on molecular programs and cellular populations is essential for comprehensively elucidating the mechanisms underlying sex disparities in health and disease.