# How relevant is the mouse model for understanding human sex determination?

## TL;DR

This study compares mouse and human gonadal sex determination at the single-cell level, revealing significant transcriptomic differences.

## Contribution

The paper provides the first comprehensive interspecies comparison of human and mouse gonadal sex determination using single-cell transcriptomics.

## Key findings

- Major transcriptomic differences exist in major cell types between human and mouse gonads.
- Only a small fraction of genes show comparable expression profiles across species.
- Poorly differentiated cells like somatic progenitors show more divergent profiles than differentiated cells.

## Abstract

The mouse is the most widely used model organism for studying mammalian gonadal sex determination and related human disorders. However, a systematic and comprehensive comparison of human and mouse sex determination processes is lacking. Here, we performed an interspecies comparative analysis of the single-cell transcriptomic atlas of gonadal sex determination in mice and humans. Our results revealed major transcriptomic differences in each of the major cell types between human and mouse gonads. Only a small fraction of these genes shared a comparable expression profile, often genes known to be essential for gonadal sex determination. While the most differentiated gonadal cell types share similar transcriptomic signatures between humans and mice, poorly differentiated cells, such as somatic progenitors, show more divergent profiles. Ultimately, these comparisons will identify the genes and pathways for which the mouse is a suitable model to study human gonadal abnormalities and optimise the use of animal models.