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The Ratio of X Chromosome to Autosomes02:45

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In most organisms, sex is determined by the ratio of X and Y chromosomes. However, in some organisms, such as Drosophila and C.elegans, sex is determined by the ratio of the number of X chromosomes to the number of sets of autosomes. The Y chromosome in Drosophila is active but does not determine sex. It contains genes responsible for the production of sperms in adult flies.  
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The Y chromosome is a sex chromosome found in several vertebrates and mammals, including humans. In addition to 22 pairs of autosomes, the human males have one X chromosome and one Y chromosome. In these organisms, the presence or absence of the Y chromosome determines the development of male traits.
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Sex differences orchestrated by androgens at single-cell resolution.

Fei Li1, Xudong Xing2, Qiqi Jin1,3,4

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This study reveals how androgens influence sex differences in complex traits by creating a single-cell atlas. Androgen modulation of immune cells offers new therapeutic targets for sex-biased diseases.

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Area of Science:

  • Genomics
  • Immunology
  • Endocrinology

Background:

  • Complex traits in mammals exhibit significant sex differences, largely influenced by androgens.
  • A comprehensive molecular and cellular understanding of these sex differences and androgen modulation is currently lacking.

Purpose of the Study:

  • To construct a high-dimensional single-cell transcriptomic atlas of 2.3 million cells from 17 tissues in Mus musculus.
  • To investigate the effects of sex and androgens on molecular programs and cellular populations.
  • To identify potential therapeutic targets for sex-biased diseases.

Main Methods:

  • Single-cell RNA sequencing (scRNA-seq) to create a transcriptomic atlas.
  • Analysis of 2.3 million cells across 17 tissues in mice.
  • Integration with UK Biobank data for disease-relevant insights.

Main Results:

  • Identified sex-biased immune gene expression and immune cell populations, including group 2 innate lymphoid cells, modulated by androgens.
  • Discovered androgen-dependent regulation of specific cellular pathways.
  • Linked findings to antigen presentation pathways and sex-biased diseases via UK Biobank data.

Conclusions:

  • The study provides a foundational molecular and cellular profile of sex differences orchestrated by androgens.
  • Androgen signaling is a key regulator of sex-biased immune responses.
  • Targeting the androgen pathway presents a potential therapeutic strategy for a range of sex-biased diseases.