Chen Siqi, Liu Ruiyang, Mo Chia-Kuei, Wendl Michael C, Houston Andrew, Lal Preet, Zhao Yanyan, Caravan Wagma, Shinkle Andrew T, Abedin-Do Atieh, Naser Al Deen Nataly, Sato Kazuhito, Li Xiang, Targino da Costa André Luiz N, Li Yize, Karpova Alla, Herndon John M, Artyomov Maxim N, Rubin Joshua B, Jain Sanjay, Li Xue, Stewart Sheila A, Ding Li, Chen Feng
Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO, USA.
Nat Genet. 2025 May;57(5):1213-1227. doi: 10.1038/s41588-025-02161-x. Epub 2025 Apr 21.
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.
许多肾脏疾病的发病率和进展存在性别差异。为了更好地理解这种性别二态性，我们整合了来自六个平台的数据，对68只小鼠在六个发育和成年时间点的76个肾脏样本进行了表征，创建了一个涵盖两性生命周期的小鼠肾脏分子图谱。我们发现，近端小管在3周龄后出现的性别差异表达基因最多，且与激素调节有关。我们揭示了雄激素和雌激素直接和间接调节的潜在机制。空间分析确定了皮质和外髓质外带中不同的性别差异空间模式。此外，老年小鼠的髓袢、近端小管和集合管中表现出更多与衰老相关的基因变化，且存在性别依赖性。我们的研究结果加深了对整个生命周期中肾脏性别二态性背后的空间分辨基因表达和激素调节的理解。
