ArticleNature communications2026
Tonicity drives collecting duct maturation in the mammalian kidney.
Daisuke Inoue, Koichiro Miike, Shunsuke Tanigawa, Kei-Ichiro Yasunaga, Rae Maeda, Tomoko Ohmori, Sayoko Fujimura, Masashi Mukoyama, Tomomi Kamba, Jose Aramburu and 4 more
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In one paragraphArticle in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 · Who and what moneyAuthors and funding
14 authors.
Daisuke InoueDepartment of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
Koichiro MiikeDepartment of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
Shunsuke TanigawaDepartment of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.ORCID 0000-0002-0642-6446 Kei-Ichiro YasunagaLiaison Laboratory Research Promotion Center, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
Rae MaedaCenter for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Tomoko OhmoriDepartment of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
Sayoko FujimuraLiaison Laboratory Research Promotion Center, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
Masashi MukoyamaDepartment of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Tomomi KambaDepartment of Urology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Jose AramburuImmunology Unit, Department of Medicine and Life Sciences, Universitat Pompeu Fabra and Barcelona Biomedical Research Park, Barcelona, Spain.ORCID 0000-0001-9279-9523 Cristina Lopez-RodriguezImmunology Unit, Department of Medicine and Life Sciences, Universitat Pompeu Fabra and Barcelona Biomedical Research Park, Barcelona, Spain.ORCID 0000-0002-2311-2406 Yuki SugiuraCenter for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine, Kyoto, Japan.ORCID 0000-0002-6983-8958 Yuichiro IzumiDepartment of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Ryuichi NishinakamuraDepartment of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan. ryuichi@kumamoto-u.ac.jp.ORCID 0000-0003-4064-2860 Funding
Japan Agency for Medical Research and Development (AMED) JP26bm1423043MEXT | Japan Society for the Promotion of Science (JSPS) JP21H05050MEXT | Japan Society for the Promotion of Science (JSPS) JP24K23941Ministry of Education, Culture, Sports, Science and Technology (MEXT) JPMXP1323015486Ministry of Education, Culture, Sports, Science and Technology (MEXT) not applicable
6 · The paper itselfAbstract
Organ maturation is a fundamental biological process and a major challenge for organoid-based regenerative medicine. During kidney maturation, osmolality increases in the renal medulla for urine concentration, yet whether this extreme environment conversely contributes to kidney maturation remains unclear. Here we show that high tonicity, i.e., salt, drives morphological, transcriptional, and functional maturation of medullary collecting ducts (CDs) primarily via nuclear factor of activated T cells 5 (NFAT5). This occurs both in vitro and in vivo. Combining high tonicity with maturation-promoting hormones, we establish a robust maturation protocol for human medullary CD organoids and a functional assay to measure water permeability in CD organoids, enabling modeling of three disease states: NFAT5 deletion, and lithium-induced and congenital nephrogenic diabetes insipidus. Collectively, high tonicity drives mammalian kidney maturation, offering a promising platform to maximize the potential of organoids for future therapies.
Indexed as
Kidney Tubules, CollectingAnimalsDiabetes Insipidus, NephrogenicHumansKidneyKidney MedullaMiceMice, KnockoutOrganoidsOsmolar Concentration
Identifiers
PMID42827133
PMCPMC13633243
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