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

Authors
 Markus M Rinschen  ;  Markus Godel  ;  Florian Grahammer  ;  Stefan Zschiedrich  ;  Martin Helmstadter  ;  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 Kuttner  ;  Melanie Boerries  ;  Hauke Busch  ;  Mario Schiffer  ;  Carsten Bergmann  ;  Marcus Kruger  ;  Friedhelm Hildebrandt  ;  Joern Dengjel  ;  Thomas Benzing  ;  Tobias B Huber 
Citation
 Cell Reports, Vol.23(8) : 2495-2508, 2018 
Journal Title
 Cell Reports 
Issue Date
2018
Keywords
end-stage renal disease ; focal segmental glomerulosclerosis ; hereditary nephrotic syndrome ; kinase ; metabolism ; proteinuria ; proteostasis ; pulse SILAC ; slit diaphragm ; systems biology
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.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/162592
Files in This Item:
T201801954.pdf Download
DOI
10.1016/j.celrep.2018.04.059
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실)
Yonsei Authors
지헌영(Gee, Heon Yung) ORCID logo https://orcid.org/0000-0002-8741-6177
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