Multi-omic and spatial analysis of mouse kidneys highlights sex-specific differences in gene regulation across the lifespan
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.
Authors
- Preet Lal (ORCID: https://orcid.org/0009-0005-8258-3688)
- Sheila A. Stewart (ORCID: https://orcid.org/0000-0002-2260-9576)
- Chia-Kuei Mo (ORCID: https://orcid.org/0009-0005-7056-0841)
- Michael C. Wendl (ORCID: https://orcid.org/0000-0002-5694-2668)
- Feng Chen (ORCID: https://orcid.org/0000-0002-2307-7954)
- Alla Karpova (ORCID: https://orcid.org/0000-0003-0467-0215)
- André Luiz N. Targino da Costa
- John M. Herndon (ORCID: https://orcid.org/0000-0002-8378-9654)
- Nataly Naser Al Deen (ORCID: https://orcid.org/0000-0003-0666-4791)
- Kazuhito Sato (ORCID: https://orcid.org/0000-0003-0589-7454)
- Joshua B. Rubin (ORCID: https://orcid.org/0000-0002-7395-1937)
- Yanyan Zhao
- Ruiyang Liu (ORCID: https://orcid.org/0000-0002-8235-3998)
- Atieh Abedin‐Do (ORCID: https://orcid.org/0000-0003-4180-8607)
- Yize Li (ORCID: https://orcid.org/0000-0003-1074-281X)
- Sanjay R. Jain (ORCID: https://orcid.org/0000-0003-2804-127X)
- Andrew Shinkle (ORCID: https://orcid.org/0000-0002-2369-9446)
- Maxim N. Artyomov (ORCID: https://orcid.org/0000-0002-1133-4212)
- Xue Li (ORCID: https://orcid.org/0000-0001-9124-9263)
- Andrew Houston (ORCID: https://orcid.org/0000-0002-3837-4695)
- Wagma Caravan (ORCID: https://orcid.org/0000-0003-4082-6723)
- Li Ding (ORCID: https://orcid.org/0000-0003-1517-2975)
- Xiang Li (ORCID: https://orcid.org/0000-0003-1199-7152)
- Siqi Chen (ORCID: https://orcid.org/0000-0002-9498-3823)
Institutions
- James S. McDonnell Foundation (US)
- Cedars-Sinai Medical Center (US)
- Washington University in St. Louis (US)
Publication Details
- Journal
- Nature Genetics
- Published
- 2025-04-21
- DOI
- https://doi.org/10.1038/s41588-025-02161-x
- Citations
- 12
- Primary Topic
- Birth, Development, and Health
- Type
- article
- Field-Weighted Citation Impact
- 41.93
Funders
- National Institutes of Health