@article{2016, keywords = {Focal segmental glomerulosclerosis, Gene expression analysis, Kidney diseases, Mass spectrometry, Proteomics}, author = {Moritz Lassé and Jamal El Saghir and Celine C. Berthier and Sean Eddy and Matthew Fischer and Sandra D. Laufer and Dominik Kylies and Arvid Hutzfeldt and Léna Lydie Bonin and Bernhard Dumoulin and Rajasree Menon and Virginia Vega-Warner and Felix Eichinger and Fadhl Alakwaa and Damian Fermin and Anja M. Billing and Akihiro Minakawa and Phillip J. McCown and Michael P. Rose and Bradley Godfrey and Elisabeth Meister and Thorsten Wiech and Mercedes Noriega and Maria Chrysopoulou and Paul Brandts and Wenjun Ju and Linda Reinhard and Elion Hoxha and Florian Grahammer and Maja T. Lindenmeyer and Tobias B. Huber and Hartmut Schlüter and Steffen Thiel and Laura H. Mariani and Victor G. Puelles and Fabian Braun and Matthias Kretzler and Fatih Demir and Jennifer L. Harder and Markus M. Rinschen}, title = {An integrated organoid omics map extends modeling potential of kidney disease}, abstract = {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.}, year = {2023}, journal = {Nature Communications}, volume = {14}, pages = {4903}, month = {2023-08-14}, issn = {2041-1723}, url = {https://www.nature.com/articles/s41467-023-39740-7}, doi = {10.1038/s41467-023-39740-7}, language = {en}, }