A multi-layered quantitative in vivo expression atlas of the podocyte unravels kidney disease candidate genes

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.

doi:10.1016/j.celrep.2018.04.059

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A multi-layered quantitative in vivo expression atlas of the podocyte unravels kidney disease candidate genes

Rinschen, Markus M. Department II of Internal Medicine, University of Cologne, Germany - Center for Molecular Medicine Cologne (CMMC), University of Cologne, Germany - CECAD, University of Cologne, Germany - Systems Biology of Ageing Cologne (Sybacol), University of Cologne, Germany -
Gödel, Markus III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany - Department of Medicine IV, University of Freiburg, Germany -
Grahammer, Florian III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany - Department of Medicine IV, University of Freiburg, Germany -
Zschiedrich, Stefan Department of Medicine IV, University of Freiburg, Germany
Helmstädter, Martin Department of Medicine IV, University of Freiburg, Germany
Kretz, Oliver III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany - Department of Medicine IV, University of Freiburg, Germany
Zarei, Mostafa Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Germany - Center for Systems Biology (ZBSA), Albert Ludwigs University, Germany
Braun, Daniela A. Division of Nephrology, Boston Children’s Hospital, Harvard Medical School, Boston, USA
Dittrich, Sebastian Department II of Internal Medicine, University of Cologne, Germany - Center for Molecular Medicine Cologne (CMMC), University of Cologne, Germany
Pahmeyer, Caroline Department II of Internal Medicine, University of Cologne, Germany - Center for Molecular Medicine Cologne (CMMC), University of Cologne, Germany
Schroder, Patricia Department of Medicine/Nephrology, Hannover Medical School, Hannover, Germany - Mount Desert Island Biological Laboratory, Salisbury Cove, ME, USA
Teetzen, Carolin Department of Medicine IV, University of Freiburg, Germany
Gee, HeonYung Mount Desert Island Biological Laboratory, Salisbury Cove, ME, USA - Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea
Daouk, Ghaleb Division of Nephrology, Boston Children’s Hospital, Harvard Medical School, Boston, USA
Pohl, Martin Department of General Pediatrics, Faculty of Medicine, University of Freiburg, Germany
Kuhn, Elisa Center for Human Genetics, Bioscientia, Ingelheim, Germany
Schermer, Bernhard Department II of Internal Medicine, University of Cologne, Germany - Center for Molecular Medicine Cologne (CMMC), University of Cologne, Germany - CECAD, University of Cologne, Germany - Systems Biology of Ageing Cologne (Sybacol), University of Cologne, Germany
Küttner, Victoria Department for Neuroanatomy, University of Freiburg, Germany - Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Germany - Department of Dermatology, Medical Center – University of Freiburg, Germany
Boerries, Melanie Systems Biology Group, Institute of Molecular Medicine, Albert Ludwigs University Freiburg, Germany - German Cancer Consortium (DKTK), Freiburg, Germany - German Cancer Research Center (DKFZ), Heidelberg, Germany
Busch, Hauke Systems Biology Group, Institute of Molecular Medicine, Albert Ludwigs University Freiburg, Germany - Lübeck Institute for Experimental Dermatology (LIED), University of Lübeck, Germany
Schiffer, Mario Department of Medicine/Nephrology, Hannover Medical School, Hannover, Germany - Mount Desert Island Biological Laboratory, Salisbury Cove, ME, USA
Bergmann, Carsten Department of Medicine IV, University of Freiburg, Germany - Center for Human Genetics, Bioscientia, Ingelheim, Germany
Krüger, Marcus Center for Molecular Medicine Cologne (CMMC), University of Cologne, Germany - CECAD, University of Cologne, Germany
Hildebrandt, Friedhelm Division of Nephrology, Boston Children’s Hospital, Harvard Medical School, Boston, USA
Dengjel, Jörn Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Germany - Center for Systems Biology (ZBSA), Albert Ludwigs University, Germany - Department of Dermatology, Medical Center – University of Freiburg, Germany - Department of Biology, University of Fribourg, Switzerland - BIOSS Centre for Biological Signaling Studies, Albert Ludwigs University Freiburg, Germany
Benzing, Thomas Department II of Internal Medicine, University of Cologne, Germany - Center for Molecular Medicine Cologne (CMMC), University of Cologne, Germany - CECAD, University of Cologne, Germany - Systems Biology of Ageing Cologne (Sybacol), University of Cologne, Germany -
Huber, Tobias B. III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany - Department of Medicine IV, University of Freiburg, Germany - Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Germany - Center for Systems Biology (ZBSA), Albert Ludwigs University, Germany - BIOSS Centre for Biological Signaling Studies, Albert Ludwigs University Freiburg, Germany -

22.05.2018

Published in:

Cell Reports. - 2018, vol. 23, no. 8, p. 2495–2508

English 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.

Faculty

Faculté des sciences et de médecine

Department

Département de Biologie

Language