Multi-omic and spatial analysis of mouse kidneys highlights sex-specific differences in gene regulation across the lifespan.

Siqi Chen, Ruiyang Liu, Chia-Kuei Mo, Michael C Wendl, Andrew Houston, Preet Lal, Yanyan Zhao, Wagma Caravan, Andrew T Shinkle, Atieh Abedin-Do, Nataly Naser Al Deen, Kazuhito Sato, Xiang Li, André Luiz N Targino da Costa, Yize Li, Alla Karpova, John M Herndon, Maxim N Artyomov, Joshua B Rubin, Sanjay Jain, Xue Li, Sheila A Stewart, Li Ding, Feng Chen

Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA. · pubmed

Paper

Abstract

There is a sex bias in the incidence and progression of many kidney diseases. To better understand such sexual dimorphism, we integrated data from six platforms, characterizing 76 kidney samples from 68 mice at six developmental and adult time points, creating a molecular atlas of the mouse kidney across the lifespan for both sexes. We show that proximal tubules have the most sex-biased differentially expressed genes emerging after 3 weeks of age and are associated with hormonal regulations. We reveal potential mechanisms involving both direct and indirect regulation by androgens and estrogens. Spatial profiling identifies distinct sex-biased spatial patterns in the cortex and outer stripe of the outer medulla. Additionally, older mice exhibit more aging-related gene alterations in loops of Henle, proximal tubules and collecting ducts in a sex-dependent manner. Our results enhance the understanding of spatially resolved gene expression and hormone regulation underlying kidney sexual dimorphism across the lifespan.

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Research summary

The paper claims that sex-specific differences in gene regulation in mouse kidneys are influenced by hormonal factors and vary across the lifespan. This research is relevant as it explores the underlying mechanisms of sexual dimorphism in kidney function, which could have implications for understanding age-related kidney diseases and their progression, thus contributing to the broader field of aging research.

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