An integrated organoid omics map extends modeling potential of kidney disease
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Published:2023-08-14
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Lassé MoritzORCID, El Saghir JamalORCID, Berthier Celine C.ORCID, Eddy SeanORCID, Fischer MatthewORCID, Laufer Sandra D.ORCID, Kylies Dominik, Hutzfeldt ArvidORCID, Bonin Léna LydieORCID, Dumoulin Bernhard, Menon Rajasree, Vega-Warner VirginiaORCID, Eichinger Felix, Alakwaa FadhlORCID, Fermin DamianORCID, Billing Anja M.ORCID, Minakawa AkihiroORCID, McCown Phillip J.ORCID, Rose Michael P.ORCID, Godfrey Bradley, Meister ElisabethORCID, Wiech ThorstenORCID, Noriega MercedesORCID, Chrysopoulou MariaORCID, Brandts PaulORCID, Ju Wenjun, Reinhard LindaORCID, Hoxha Elion, Grahammer Florian, Lindenmeyer Maja T.ORCID, Huber Tobias B.ORCID, Schlüter HartmutORCID, Thiel SteffenORCID, Mariani Laura H., Puelles Victor G.ORCID, Braun FabianORCID, Kretzler MatthiasORCID, Demir FatihORCID, Harder Jennifer L.ORCID, Rinschen Markus M.ORCID
Abstract
AbstractKidney organoids are a promising model to study kidney disease, but their use is constrained by limited knowledge of their functional protein expression profile. Here, we define the organoid proteome and transcriptome trajectories over culture duration and upon exposure to TNFα, a cytokine stressor. Older organoids increase deposition of extracellular matrix but decrease expression of glomerular proteins. Single cell transcriptome integration reveals that most proteome changes localize to podocytes, tubular and stromal cells. TNFα treatment of organoids results in 322 differentially expressed proteins, including cytokines and complement components. Transcript expression of these 322 proteins is significantly higher in individuals with poorer clinical outcomes in proteinuric kidney disease. Key TNFα-associated protein (C3 and VCAM1) expression is increased in both human tubular and organoid kidney cell populations, highlighting the potential for organoids to advance biomarker development. By integrating kidney organoid omic layers, incorporating a disease-relevant cytokine stressor and comparing with human data, we provide crucial evidence for the functional relevance of the kidney organoid model to human kidney disease.
Funder
U.S. Department of Health & Human Services | National Institutes of Health
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference83 articles.
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