A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes

  • Markus M Rinschen
  • Markus Gödel (Geteilte/r Erstautor/in)
  • Florian Grahammer
  • Stefan Zschiedrich
  • Martin Helmstädter
  • Oliver Kretz
  • Mostafa Zarei
  • Daniela A Braun
  • Sebastian Dittrich
  • Caroline Pahmeyer
  • Patricia Schroder
  • Carolin Teetzen
  • HeonYung Gee
  • Ghaleb Daouk
  • Martin Pohl
  • Elisa Kuhn
  • Bernhard Schermer
  • Victoria Küttner
  • Melanie Boerries
  • Hauke Busch
  • Mario Schiffer
  • Carsten Bergmann
  • Marcus Krüger
  • Friedhelm Hildebrandt
  • Joern Dengjel
  • Thomas Benzing
  • Tobias B Huber

Beteiligte Einrichtungen


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.

Bibliografische Daten

StatusVeröffentlicht - 22.05.2018
PubMed 29791858