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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 -
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    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
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/307069
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