圣路易斯的华盛顿大学陈峰团队揭示了小鼠肾脏的多组学和空间分析强调了基因调控在整个生命周期中的性别特异性差异。2025年4月21日，国际知名学术期刊《自然—遗传学》发表了这一成果。

为了更好地理解这种两性二态性，该研究组整合了来自6个平台的数据，在6个发育和成年时间点对68只小鼠的76个肾脏样本进行了表征，创建了一个跨两性寿命的无主题肾脏分子图谱。研究团队发现，近端小管在3岁后出现的性别差异表达基因最多。周龄和与荷尔蒙调节有关。该课题组研究人员揭示了雄激素和雌激素直接和间接调节的潜在机制。空间分析在皮层和外髓质的外条纹中识别出明显的性别偏向的空间模式。此外，老年小鼠在Henle环、近端小管和收集管中以性别依赖的方式表现出更多与衰老相关的基因改变。他们的研究结果增强了对肾脏性别二态性的空间解析基因表达和激素调控的理解。

研究人员表示，许多肾脏疾病的发病率和进展存在性别偏见。

附：英文原文

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

Author: 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, Andr 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

Issue&Volume: 2025-04-21

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 3weeks 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.

DOI: 10.1038/s41588-025-02161-x

Source: https://www.nature.com/articles/s41588-025-02161-x