TY - JOUR
KW - Focal segmental glomerulosclerosis
KW - Gene expression analysis
KW - Kidney diseases
KW - Mass spectrometry
KW - Proteomics
AU - Moritz Lassé
AU - Jamal El Saghir
AU - Celine C. Berthier
AU - Sean Eddy
AU - Matthew Fischer
AU - Sandra D. Laufer
AU - Dominik Kylies
AU - Arvid Hutzfeldt
AU - Léna Lydie Bonin
AU - Bernhard Dumoulin
AU - Rajasree Menon
AU - Virginia Vega-Warner
AU - Felix Eichinger
AU - Fadhl Alakwaa
AU - Damian Fermin
AU - Anja M. Billing
AU - Akihiro Minakawa
AU - Phillip J. McCown
AU - Michael P. Rose
AU - Bradley Godfrey
AU - Elisabeth Meister
AU - Thorsten Wiech
AU - Mercedes Noriega
AU - Maria Chrysopoulou
AU - Paul Brandts
AU - Wenjun Ju
AU - Linda Reinhard
AU - Elion Hoxha
AU - Florian Grahammer
AU - Maja T. Lindenmeyer
AU - Tobias B. Huber
AU - Hartmut Schlüter
AU - Steffen Thiel
AU - Laura H. Mariani
AU - Victor G. Puelles
AU - Fabian Braun
AU - Matthias Kretzler
AU - Fatih Demir
AU - Jennifer L. Harder
AU - Markus M. Rinschen
AB - 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.
BT - Nature Communications
DA - 2023-08-14
DO - 10.1038/s41467-023-39740-7
IS - 1
LA - en
N2 - 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.
PY - 2023
EP - 4903
T2 - Nature Communications
TI - An integrated organoid omics map extends modeling potential of kidney disease
UR - https://www.nature.com/articles/s41467-023-39740-7
VL - 14
Y2 - 2023-09-15
SN - 2041-1723
ER -