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An integrated organoid omics map extends modeling potential of kidney disease

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

DOI

  • Moritz Lassé, University Medical Center Hamburg-Eppendorf
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  • Jamal El Saghir, University of Michigan, Ann Arbor
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  • Celine C Berthier, University of Michigan, Ann Arbor
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  • Sean Eddy, University of Michigan, Ann Arbor
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  • Matthew Fischer, University of Michigan, Ann Arbor
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  • Sandra D Laufer, University Medical Center Hamburg-Eppendorf
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  • Dominik Kylies, University Medical Center Hamburg-Eppendorf
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  • Arvid Hutzfeldt, University Medical Center Hamburg-Eppendorf
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  • Léna Lydie Bonin, Aarhus Universitet
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  • Bernhard Dumoulin, University Medical Center Hamburg-Eppendorf
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  • Rajasree Menon, University of Michigan, Ann Arbor
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  • Virginia Vega-Warner, University of Michigan, Ann Arbor
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  • Felix Eichinger, University of Michigan, Ann Arbor
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  • Fadhl Alakwaa, University of Michigan, Ann Arbor
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  • Damian Fermin, University of Michigan, Ann Arbor
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  • Anja M Billing
  • Akihiro Minakawa, University of Michigan, Ann Arbor
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  • Phillip J McCown, University of Michigan, Ann Arbor
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  • Michael P Rose, University of Michigan, Ann Arbor
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  • Bradley Godfrey, University of Michigan, Ann Arbor
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  • Elisabeth Meister, University Medical Center Hamburg-Eppendorf
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  • Thorsten Wiech, University Medical Center Hamburg-Eppendorf
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  • Mercedes Noriega, University Medical Center Hamburg-Eppendorf
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  • Maria Chrysopoulou
  • Paul Brandts, University Medical Center Hamburg-Eppendorf
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  • Wenjun Ju, University of Michigan, Ann Arbor
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  • Linda Reinhard, University Medical Center Hamburg-Eppendorf
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  • Elion Hoxha, University Medical Center Hamburg-Eppendorf
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  • Florian Grahammer, University Medical Center Hamburg-Eppendorf
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  • Maja T Lindenmeyer, University Medical Center Hamburg-Eppendorf
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  • Tobias B Huber, University Medical Center Hamburg-Eppendorf
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  • Hartmut Schlüter, University Medical Center Hamburg-Eppendorf
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  • Steffen Thiel
  • Laura H Mariani, University of Michigan, Ann Arbor
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  • Victor G Puelles
  • Fabian Braun, University Medical Center Hamburg-Eppendorf
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  • Matthias Kretzler, University of Michigan, Ann Arbor
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  • Fatih Demir
  • Jennifer L Harder, University of Michigan, Ann Arbor
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  • Markus M Rinschen

Kidney 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.

OriginalsprogEngelsk
Artikelnummer4903
TidsskriftNature Communications
Vol/bind14
Nummer1
Antal sider21
ISSN2041-1723
DOI
StatusUdgivet - aug. 2023

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