Rinschen, Markus M., Goedel, Markus, Grahammer, Florian, Zschiedrich, Stefan, Helmstaedter, Martin, Kretz, Oliver, Zarei, Mostafa, Braun, Daniela A., Dittrich, Sebastian, Pahmeyer, Caroline, Schroder, Patricia, Teetzen, Carolin, Gee, HeonYung, Daouk, Ghaleb, Pohl, Martin, Kuhn, Elisa, Schermer, Bernhard ORCID: 0000-0002-5194-9000, Kuettner, Victoria, Boerries, Melanie, Busch, Hauke ORCID: 0000-0003-4763-4521, Schiffer, Mario ORCID: 0000-0002-8414-1470, Bergmann, Carsten, Krueger, Marcus, Hildebrandt, Friedhelm, Dengjel, Joern ORCID: 0000-0002-9453-4614, Benzing, Thomas and Huber, Tobias B. ORCID: 0000-0001-7175-5062 (2018). A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes. Cell Reports, 23 (8). S. 2495 - 2509. CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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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 knock-down 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Rinschen, Markus M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goedel, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grahammer, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zschiedrich, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Helmstaedter, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kretz, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zarei, MostafaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Braun, Daniela A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dittrich, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pahmeyer, CarolineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schroder, PatriciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teetzen, CarolinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gee, HeonYungUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Daouk, GhalebUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pohl, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuhn, ElisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schermer, BernhardUNSPECIFIEDorcid.org/0000-0002-5194-9000UNSPECIFIED
Kuettner, VictoriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boerries, MelanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Busch, HaukeUNSPECIFIEDorcid.org/0000-0003-4763-4521UNSPECIFIED
Schiffer, MarioUNSPECIFIEDorcid.org/0000-0002-8414-1470UNSPECIFIED
Bergmann, CarstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krueger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hildebrandt, FriedhelmUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dengjel, JoernUNSPECIFIEDorcid.org/0000-0002-9453-4614UNSPECIFIED
Benzing, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huber, Tobias B.UNSPECIFIEDorcid.org/0000-0001-7175-5062UNSPECIFIED
URN: urn:nbn:de:hbz:38-186049
DOI: 10.1016/j.celrep.2018.04.059
Journal or Publication Title: Cell Reports
Volume: 23
Number: 8
Page Range: S. 2495 - 2509
Date: 2018
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 2211-1247
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
FOCAL SEGMENTAL GLOMERULOSCLEROSIS; RESISTANT NEPHROTIC SYNDROME; SLIT DIAPHRAGM; FILTRATION BARRIER; PROTEOMIC ANALYSIS; TYROSINE KINASE; PHOSPHOPROTEOMIC ANALYSIS; REGULATORY MECHANISMS; COPY-NUMBER; CELLMultiple languages
Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/18604

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