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Abstract: TH-PO793

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

Session Information

Category: Glomerular Diseases

  • 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix

Authors

  • Rinschen, Markus M., CECAD, Cologne, Germany
  • Grahammer, Florian, University Hospital Hamburg-Eppendorf, Hamburg, Germany
  • Benzing, Thomas, University of Cologne, Köln, Germany
  • Huber, Tobias B., University Medical Center Hamburg, Hamburg, Germany
Background

Damage to and loss of glomerular podocytes has been identified as the culprit lesion in progressive kidney diseases. The molecular identity of podocytes is currently not known.

Methods

We combine deep mass spectrometry-based proteomics with mRNA sequencing, bioinformatics, and hypothesis-driven studies to provide a comprehensive and quantitative map of mammalian podocytes

Results

The analyses identified unanticipated signaling pathways in podocytes. 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. FARP1 is a potentially mechanosensitive proteins that links the actin cytoskeleton to the membrane.

Conclusion

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.

Funding

  • Government Support - Non-U.S.