Rinschen, Markus M. Gödel, Markus Grahammer, Florian Zschiedrich, Stefan Helmstädter, Martin Kretz, Oliver Zarei, Mostafa Braun, Daniela A. Dittrich, Sebastian Pahmeyer, Caroline Schroder, Patricia Teetzen, Carolin Gee, HeonYung Daouk, Ghaleb Pohl, Martin Kuhn, Elisa Schermer, Bernhard Küttner, Victoria Boerries, Melanie Busch, Hauke Schiffer, Mario Bergmann, Carsten Krüger, Marcus Hildebrandt, Friedhelm Dengjel, Jörn Benzing, Thomas Huber, Tobias B. 2018-05-22 Damage to and loss of glomerular podocytes has been identified as the culprit lesion in progressive kidney diseases. Here, we combine mass spectrometry-based proteomics with mRNA sequencing, bioinformatics, and hypothesis-driven studies to provide a comprehensive and quantitative map of mammalian podocytes that identifies unanticipated signaling pathways. Comparison of the in vivo datasets with proteomics data from podocyte cell cultures showed a limited value of available cell culture models. Moreover, in vivo stable isotope labeling by amino acids uncovered surprisingly rapid synthesis of mitochondrial proteins under steady-state conditions that was perturbed under autophagy-deficient, disease-susceptible conditions. Integration of acquired omics dimensions suggested FARP1 as a candidate essential for podocyte function, which could be substantiated by genetic analysis in humans and knockdown experiments in zebrafish. This work exemplifies how the integration of multi-omics datasets can identify a framework of cell-type-specific features relevant for organ health and disease. application/pdf https://folia.unifr.ch/global/documents/307069 https://folia.unifr.ch/documents/307069/files/den_mlq.pdf https://folia.unifr.ch/documents/307069/files/den_mlq_sm.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2018.04.059 info:eu-repo/semantics/openAccess License undefined Cell Reports. - 2018, vol. 23, no. 8, p. 2495–2508 info:eu-repo/classification/udc/57 A multi-layered quantitative in vivo expression atlas of the podocyte unravels kidney disease candidate genes http://purl.org/coar/resource_type/c_6501