A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes
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A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes. / Rinschen, Markus M; Gödel, Markus; Grahammer, Florian; Zschiedrich, Stefan; Helmstädter, 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; Küttner, Victoria; Boerries, Melanie; Busch, Hauke; Schiffer, Mario; Bergmann, Carsten; Krüger, Marcus; Hildebrandt, Friedhelm; Dengjel, Joern; Benzing, Thomas; Huber, Tobias B.
in: CELL REP, Jahrgang 23, Nr. 8, 22.05.2018, S. 2495-2508.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes
AU - Rinschen, Markus M
AU - Gödel, Markus
AU - Grahammer, Florian
AU - Zschiedrich, Stefan
AU - Helmstädter, Martin
AU - Kretz, Oliver
AU - Zarei, Mostafa
AU - Braun, Daniela A
AU - Dittrich, Sebastian
AU - Pahmeyer, Caroline
AU - Schroder, Patricia
AU - Teetzen, Carolin
AU - Gee, HeonYung
AU - Daouk, Ghaleb
AU - Pohl, Martin
AU - Kuhn, Elisa
AU - Schermer, Bernhard
AU - Küttner, Victoria
AU - Boerries, Melanie
AU - Busch, Hauke
AU - Schiffer, Mario
AU - Bergmann, Carsten
AU - Krüger, Marcus
AU - Hildebrandt, Friedhelm
AU - Dengjel, Joern
AU - Benzing, Thomas
AU - Huber, Tobias B
N1 - Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2018/5/22
Y1 - 2018/5/22
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1016/j.celrep.2018.04.059
DO - 10.1016/j.celrep.2018.04.059
M3 - SCORING: Journal article
C2 - 29791858
VL - 23
SP - 2495
EP - 2508
JO - CELL REP
JF - CELL REP
SN - 2211-1247
IS - 8
ER -