Multiomic And Spatial Analysis Of Mouse Kidneys Highlights Sexspecific Differences In Gene Regulation Across The Lifespan Siqi Chen1 by Siqi Chen1, 2, 12, Ruiyang Liu1, 2, 12, Chia-kuei Mo1, 2, 12, Michael C. Wendl1, 2, 3, instant download after payment.

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 diferentially 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 profling identifes 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.