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

Cell Rep. 2018 May 22;23(8):2495-2508. doi: 10.1016/j.celrep.2018.04.059.


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.

Keywords: end-stage renal disease; focal segmental glomerulosclerosis; hereditary nephrotic syndrome; kinase; metabolism; proteinuria; proteostasis; pulse SILAC; slit diaphragm; systems biology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cells, Cultured
  • Gene Expression Regulation*
  • Genetic Association Studies*
  • Humans
  • Kidney Diseases / genetics*
  • Mice
  • Podocytes / metabolism*
  • Proteome / metabolism
  • Transcriptome / genetics
  • Zebrafish


  • Proteome