PUBLICATION

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

Authors
Rinschen, M.M., Gödel, M., Grahammer, F., Zschiedrich, S., Helmstädter, M., Kretz, O., Zarei, M., Braun, D.A., Dittrich, S., Pahmeyer, C., Schroder, P., Teetzen, C., Gee, H., Daouk, G., Pohl, M., Kuhn, E., Schermer, B., Küttner, V., Boerries, M., Busch, H., Schiffer, M., Bergmann, C., Krüger, M., Hildebrandt, F., Dengjel, J., Benzing, T., Huber, T.B.
ID
ZDB-PUB-180526-7
Date
2018
Source
Cell Reports   23: 2495-2508 (Journal)
Registered Authors
Bergmann, Carsten, Hildebrandt, Friedhelm
Keywords
end-stage renal disease, focal segmental glomerulosclerosis, hereditary nephrotic syndrome, kinase, metabolism, proteinuria, proteostasis, pulse SILAC, slit diaphragm, systems biology
MeSH Terms
  • Proteome/metabolism
  • Cells, Cultured
  • Humans
  • Podocytes/metabolism*
  • Genetic Association Studies*
  • Base Sequence
  • Zebrafish
  • Animals
  • Kidney Diseases/genetics*
  • Transcriptome/genetics
  • Mice
  • Gene Expression Regulation*
(all 12)
PubMed
29791858 Full text @ Cell Rep.
Abstract
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.
Genes / Markers
Figures
Figure Gallery (1 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
lri500Tg + MO1-farp1standard conditionsDay 4 to Day 5
lri500Tg + MO1-farp1standard conditionsDay 5
lri500Tg + MO1-farp1standard conditionsDay 5
lri500Tg + MO1-farp1standard conditionsDay 5
lri500Tg + MO1-farp1standard conditionsDay 5
1 - 5 of 5
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
lri500TgTransgenic Insertion
    1 - 1 of 1
    Show
    Human Disease / Model
    Human Disease Fish Conditions Evidence
    focal segmental glomerulosclerosisTAS
    1 - 1 of 1
    Show
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    farp1MO1-farp1MRPHLNO
    1 - 1 of 1
    Show
    Fish
    Fish
    lri500Tg + MO1-farp1
    1 - 1 of 1
    Show
    Antibodies
    No data available
    Orthology
    Gene Orthology
    farp1
    1 - 1 of 1
    Show
    Engineered Foreign Genes
    Marker Marker Type Name
    EGFPEFGEGFP
    1 - 1 of 1
    Show
    Mapping
    No data available
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    Citation
    Rinschen, M.M., Gödel, M., Grahammer, F., Zschiedrich, S., Helmstädter, M., Kretz, O., Zarei, M., Braun, D.A., Dittrich, S., Pahmeyer, C., Schroder, P., Teetzen, C., Gee, H., Daouk, G., Pohl, M., Kuhn, E., Schermer, B., Küttner, V., Boerries, M., Busch, H., Schiffer, M., Bergmann, C., Krüger, M., Hildebrandt, F., Dengjel, J., Benzing, T., Huber, T.B. (2018) A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes. Cell Reports. 23:2495-2508.