Cited by 105Renal Diseases and GlomerulopathiesAdvanced Proteomics Techniques and ApplicationsRenal and related cancers

The DOI matches its Crossref record; 84 of the 84 references it cites were found in a registry or an index; none of the 53 sources its claims cite is checked for support yet.

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

Open access

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.·2018·Cell Reports

DOI 10.1016/j.celrep.2018.04.059PMC PMC5986710

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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 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.

AI snapshot

Written from the paper’s full text.

TL;DR

This study combines quantitative in vivo proteomics, mRNA sequencing, and dynamic stable isotope labeling to build a multi-layered atlas of mouse podocytes and glomerular non-podocytes. Integrating these datasets identifies podocyte-enriched proteins, cell-culture artifacts, proteostatic features, and FARP1 as a candidate nephrotic syndrome gene.

Key findings

Deep mapping identified more than 9,000 proteins, with absolute quantification of 6,979 proteins; 551 proteins were significantly podocyte-enriched. Disease-associated genes comprised 35 of 7,000 (0.5%) quantified proteins but contributed approximately 4% of podocyte protein mass, and the slit diaphragm complex podocin-Neph1-Nephrin-Fat1 showed a copy-number ratio of ∼10:2:1:0.5.
Podocyte mRNA and protein abundances correlated only weakly overall (Pearson’s R = 0.47), though the correlation was stronger for podocytes than non-podocytes; 2D enrichment showed ECM proteins decreased and metabolic proteins stabilized relative to mRNA.
In vivo stable isotope labeling revealed rapid synthesis of mitochondrial proteins under steady-state conditions; ATG5 podocyte-specific knockout podocytes showed significantly lower incorporation of ER proteins and significantly higher incorporation of mitochondrial proteins compared with controls.
Multi-omics integration nominated FARP1: a homozygous FARP1 mutation was found in one family with nephrotic syndrome, and farp1 knockdown in zebrafish larvae caused pericardial edema and proteinuria.

Methods

Podocytes and non-podocyte glomerular cells were isolated by FACS from hNPHS2Cre∗mT/mG mice, then analyzed by mass spectrometry-based proteomics, mRNA sequencing, and bioinformatics; absolute protein quantification used iBAQ and the proteomic ruler.
In vivo stable isotope labeling used adult mice fed 13C6-lysine for 1, 2, and 3 weeks, with hierarchical clustering of heavy/light ratios and comparison to ATG5 podocyte-specific knockout mice.
Cultured mouse and human podocytes were compared with native podocytes, including growth on soft matrices with an elastic modulus of 12 kPa; human genetic screening used exome sequencing of 430 families with hereditary nephrotic syndrome and a second cohort of 700 patients with nephrotic syndrome.

Limitations

Stated: stable isotope incorporation data “do not strictly correlate with a protein ‘half-life’ because of intracellular amino acid recycling”; several known podocyte genes, such as Trpc6, were identified but could not be quantified because of low abundance; the second FARP1 patient’s alleles could not be confirmed to segregate because family DNA was unavailable; and the ATG5-related mitochondrial findings “need further corroboration.”
Evident from the text: the human genetic evidence for FARP1 is limited to one homozygous family plus a second heterozygous patient with unclear segregation, and the functional support comes from zebrafish knockdown rather than rescue experiments.
Evident from the text: the cell-culture comparison relies on a previously published immortalized mouse podocyte line, and the paper notes that soft-matrix culture does not restore podocyte-specific actin binders or membrane proteins.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.celrep.2018.04.059

Cites

84 of 84 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 53 cited sources checked · 0 supported · 0 flagged

In the paper
“among these were many gene products currently known to be associated with hereditary nephrotic syndrome (Sadowski et al., 2015).”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Results > Determination of Podocyte-Enriched Proteins
What the sources say
- Not checked yetcites Sadowski et al., 2015 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“A systematic Medline search of these 190 proteins revealed that the majority were not explicitly linked to podocytes (Table S4).”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Results > Determination of Podocyte-Enriched Proteins
What the sources say
- Not checked yetcites Uhlén et al., 2015 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“Enrichment analyses demonstrated overrepresentation of several known pathways enriched on mRNA levels, among these extracellular matrix (ECM) synthesis and nephrin interactions (Figure 2B; Figures S2E–S2I; Brunskill et al., 2011).”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Results > Integration of Deep Transcriptomic and Proteomics Data
What the sources say
- Not checked yetcites Brunskill et al., 2011 source
Strength:boosted· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here we gained a near-comprehensive view of the static and dynamic podocyte proteome and transcriptome by applying recently developed technologies”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Discussion
Load-bearingStrength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Rests on an assumption: The podocyte is a central gatekeeper to prevent proteinuria and renal failure.
- Rests on an assumption: Interrogation of individual cell types at multiple omics levels can yield insights into both essential molecular components and preventive strategies.
None of the sources cited for this claim have been checked yet.
In the paper
“Indeed, transcript levels can only explain one- to two-thirds of protein levels, underlining the importance of post-transcriptional control (Liu et al., 2016, Vogel and Marcotte, 2012).”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Introduction
What the sources say
- Not checked yetcites Liu et al., 2016 source
- Not checked yetcites Vogel and Marcotte, 2012 source
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“However, several studies from different fields found that absolute abundances of mRNA and protein abundances correlate only moderately.”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Introduction
What the sources say
- Not checked yetcites Liu et al., 2016 source
- Not checked yetcites Vogel and Marcotte, 2012 source
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Interference with any of these functions—for instance, as an inherited gene defect in humans (Boute et al., 2000, Kaplan et al., 2000, Kestilä et al., 1998, Reiser et al., 2005)—leads to proteinuria, podocyte loss, glomerular scarring and, ultimately, chronic kidney disease.”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Introduction
What the sources say
- Not checked yetcites Boute et al., 2000 source
- Not checked yetcites Kaplan et al., 2000 source
- Not checked yetcites Kestilä et al., 1998 source
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
In the paper
“Podocytes are essential to maintain a physiological blood-urine barrier (Pavenstädt et al., 2003)”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Introduction
What the sources say
- Not checked yetcites Pavenstädt et al., 2003 source
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“all four have reported relevance for podocyte biology (Harita et al., 2008, New et al., 2014, Schmieder et al., 2004)”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Results > Determination of Podocyte-Enriched Proteins
What the sources say
- Not checked yetcites Harita et al., 2008 source
- Not checked yetcites New et al., 2014 source
- Not checked yetcites Schmieder et al., 2004 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“This elastic modulus (“stiffness”) of 12 kPa is similar to that of a skeletal muscle cell, a mechanically challenged cell (Gilbert et al., 2010, Janmey and Miller, 2011).”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Results > Comparison of the Deep Native Podocyte Proteome with the Cultured Podocyte Proteome
What the sources say
- Not checked yetcites Gilbert et al., 2010 source
- Not checked yetcites Janmey and Miller, 2011
Load-bearingStrength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
In the paper
“indicating that podocin is by far the most abundant slit diaphragm protein within podocytes (Grahammer et al., 2013).”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Results > Absolute Quantification of the Native Podocyte Proteome
What the sources say
- Not checked yetcites Grahammer et al., 2013 source
Strength:hedged· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“podocytes strongly react to other mechanical cues, such as hydrostatic pressure (Kriz and Lemley, 2015), stretch (Durvasula et al., 2004, Kim et al., 2013, Petermann et al., 2005), or membrane curvature (Inoue and Ishibe, 2015), in vitro and in vivo”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Discussion
What the sources say
- Not checked yetcites Kriz and Lemley, 2015
- Not checked yetcites Durvasula et al., 2004 source
- Not checked yetcites Inoue and Ishibe, 2015
Strength:boosted· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here we demonstrate that such a comprehensive atlas of protein and mRNA expression datasets now allows distilling molecular characteristic features of podocytes, ultimately up to the prediction of candidate genes associated with human disease.”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Discussion
Load-bearingStrength:boosted· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Rests on an assumption: The podocyte is a central gatekeeper to prevent proteinuria and renal failure.
- Rests on an assumption: Interrogation of individual cell types at multiple omics levels can yield insights into both essential molecular components and preventive strategies.
None of the sources cited for this claim have been checked yet.
In the paper
“Single-cell podocyte sorting previously enabled only incomplete in vivo analysis of the podocyte proteome”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Discussion
What the sources say
- Not checked yetcites Boerries et al., 2013 source
- Not checked yetcites Rinschen et al., 2015a
- Not checked yetcites Rinschen et al., 2016a
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes

It may state two separate claims as one. 25
The quote only partly states this claim. 1
Probably not a substantial claim. 25

In the paper
“Two clusters showed differences between 33°C and 37°C and native cells; these were, as expected (Rinschen et al., 2016b), related to the cell cycle (Figure 4C).”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Results > Comparison of the Deep Native Podocyte Proteome with the Cultured Podocyte Proteome
What the sources say
- Not checked yetcites Rinschen et al., 2016b
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
In the paper
“This candidate gene, and the genes identified in a recent population-based study (Yu et al., 2016), clustered close to known disease genes (Figure 6A), and all shared high Z scores in at least three of the four parameters analyzed (Figure 6B).”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Results > Multi-omics Integration Reveals Candidate Genes for Podocyte Function in Humans
What the sources say
- Not checked yetcites Yu et al., 2016
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition, in vivo stable amino acid isotope labeling strategies opened new avenues for the quantification of protein dynamics when used in pulse experiments (Krüger et al., 2008, Savas et al., 2012, Toyama et al., 2013).”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Introduction
What the sources say
- Not checked yetcites Krüger et al., 2008 source
- Not checked yetcites Savas et al., 2012 source
- Not checked yetcites Toyama et al., 2013 source
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“As a result, proteins can be resolved and quantified relatively and absolutely, culminating in a near-comprehensive mass spectrometry-based expression map of the human proteome (Kim et al., 2014, Wilhelm et al., 2014).”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Introduction
What the sources say
- Not checked yetcites Kim et al., 2014 source
- Not checked yetcites Wilhelm et al., 2014 source
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This proteomics parameter is relative to copy numbers in a given sample (Kohli et al., 2014, Schwanhäusser et al., 2011).”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Results > Absolute Quantification of the Native Podocyte Proteome
What the sources say
- Not checked yetcites Kohli et al., 2014 source
- Not checked yetcites Schwanhäusser et al., 2011 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The incorporation of this essential amino acid should correlate with the dynamic synthesis rate (although these data do not strictly correlate with a protein “half-life” because of intracellular amino acid recycling (Krüger et al., 2008)).”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Results > Analysis of Podocyte Proteome Dynamics and Integration with Deep Proteomics Mapping
What the sources say
- Not checked yetcites Krüger et al., 2008 source
Load-bearingStrength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“Podocyte protein homeostasis largely depends on signaling mediated via posttranslational modifications, such as phosphorylation, ubiquitylation, acetylation, and proteolytic processing (New et al., 2014).”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Results > Determination of Podocyte-Enriched Proteins
What the sources say
- Not checked yetcites New et al., 2014 source
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The ATG5 pKO allele makes podocytes extremely susceptible to damage (Hartleben et al., 2010).”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Results > Analysis of Podocyte Proteome Dynamics and Integration with Deep Proteomics Mapping
What the sources say
- Not checked yetcites Hartleben et al., 2010 source
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Still, proteins synthesized rapidly should exhibit a high heavy amino acid incorporation rate (and a high heavy/light [H/L] ratio), whereas stable, “long-lived” proteins with slow translation should have a lower incorporation rate (Savas et al., 2012).”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Results > Analysis of Podocyte Proteome Dynamics and Integration with Deep Proteomics Mapping
What the sources say
- Not checked yetcites Savas et al., 2012 source
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“a similar number of proteins has been shown to be expressed in native neurons”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Discussion
What the sources say
- Not checked yetcites Sharma et al., 2015 source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“a finding that could be caused by stiffness of the cell culture dish”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Discussion
What the sources say
- Not checked yetcites Gilbert et al., 2010 source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“At least 10,000 proteins are suggested to be expressed in a cultured cell line”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Discussion
What the sources say
- Not checked yetcites Kulak et al., 2014 source
- Not checked yetcites Mann et al., 2013 source
- Not checked yetcites Nagaraj et al., 2011 source
Strength:hedged· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Several of the proteins, but by far not all of them, have already been studied in podocytes and have been linked in part by dramatic phenotypes in conditional and targeted mouse models (e.g., protein kinase C) (Huber et al., 2009) or human patients (e.g., MAGI2; Bierzynska et al., 2016).”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Discussion
What the sources say
- Not checked yetcites Huber et al., 2009 source
- Not checked yetcites Bierzynska et al., 2016 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, the podocyte has an overall low abundance of mitochondrial proteins but high mitochondrial resynthesis and, assuming a steady-state equilibrium, also turnover.”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Discussion
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- The authors state this as an assumption: The podocyte is in a steady-state equilibrium with respect to mitochondrial protein synthesis and degradation.
None of the sources cited for this claim have been checked yet.
In the paper
“Cultured podocytes are widely used to investigate podocyte damage and serve as a model to study the regulation of the cytoskeleton and many other aspects of podocyte biology”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Discussion
What the sources say
- Not checked yetcites Lee et al., 2015a
- Not checked yetcites Shankland, 2006 source
- Not checked yetcites Yu et al., 2013
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“ATG5, a protein essential for autophagy”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Discussion
What the sources say
- Not checked yetcites Hartleben et al., 2010 source
Load-bearingStrength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“The leading edge is a long-established model to study the cell biology of podocyte foot processes, and eventual slit diaphragm signaling”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Discussion
What the sources say
- Not checked yetcites Garg and Holzman, 2012
- Not checked yetcites Garg et al., 2010 source
- Not checked yetcites Moeller et al., 2004 source
Strength:boosted· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“many of these proteins oppose the formation of stress fibers by promoting actin branching to promote a “motile” phenotype”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Discussion
What the sources say
- Not checked yetcites Higgs and Pollard, 2001
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The concept presented here will be advantageous for understanding cell-type-specific function in health and disease.”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Discussion
Load-bearingStrength:plain· not yet calibrated
Tests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passes
Probably not a substantial claim. It may be too vague to check against evidence.
- Rests on an assumption: The podocyte is a central gatekeeper to prevent proteinuria and renal failure.
- Rests on an assumption: Interrogation of individual cell types at multiple omics levels can yield insights into both essential molecular components and preventive strategies.
In the paper
“specific members of the tetraspanin family, which were confirmed in Drosophila nephrocyte studies as highly conserved functional regulators of filtering cells”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Discussion
What the sources say
- Not checked yetcites Sachs et al., 2012 source
Strength:boosted· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“a key molecule controlling mitophagy”
§ A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes > Discussion
What the sources say
- Not checked yetcites Narendra et al., 2008 source
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
Probably not a substantial claim.

49 of 49

The paper relies on this without support.
Damage to and loss of glomerular podocytes is the culprit lesion in progressive kidney diseases.
“Damage to and loss of glomerular podocytes has been identified as the culprit lesion in progressive kidney diseases.”
The paper relies on this without support.
Deterioration of podocyte function and subsequent proteinuria are critical accelerators of renal functional decline in disease states.
“deterioration of podocyte function and subsequent proteinuria are critical accelerators of renal functional decline in disease states.”
The paper relies on this without support.
The molecular identity of the podocyte is not defined.
“the molecular identity of the podocyte is not defined”
The paper relies on this without support.
It is unclear how podocyte function could be targeted therapeutically.
“it is unclear how its function could be targeted therapeutically.”
The paper relies on this without support.
The podocyte needs to maintain its proteome because of considerable metabolic and mechanical stress, and this is a prerequisite to maintain its architecture, cytoskeletal integrity, signal transduction, and metabolic function.
“Because of considerable metabolic and mechanical stress, the podocyte needs to maintain its proteome—a prerequisite to maintain its architecture, cytoskeletal integrity, signal transduction, and metabolic function.”
The paper relies on this without support.
Most genes mutated in genetic forms of proteinuria or nephrotic syndrome encode podocyte-enriched genes.
“Most of the genes mutated in genetic forms of proteinuria or nephrotic syndrome encode for podocyte-enriched genes.”
The paper relies on this without support.
Podocyte cell cultures are a commonly used tool in podocyte research.
“a commonly used tool in podocyte research.”
The authors state this as an assumption.
The podocyte is in a steady-state equilibrium with respect to mitochondrial protein synthesis and degradation.
“assuming a steady-state equilibrium”
The paper relies on this without support.
The podocyte is a central gatekeeper to prevent proteinuria and renal failure.
“the podocyte has emerged as a central gatekeeper to prevent proteinuria and renal failure, two unmet and frequent clinical symptoms associated with dramatically increased cardiovascular risk.”
The paper relies on this without support.
Interrogation of individual cell types at multiple omics levels can yield insights into both essential molecular components and preventive strategies.
“Interrogation of individual cell types at multiple omics levels can yield insights into both essential molecular components and preventive strategies.”

10 of 10

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

Figure 4B reverses which sample has lower protein abundance
Minor
The results text says the Figure 4B clusters have lower abundance in cultured cells than in native podocytes. The caption says abundance is lower in native podocytes than in cultured podocytes.
Figure 3D is described as both enriched and de-enriched
Minor
The results text assigns enriched protein categories to Figure 3D, whereas the caption describes Figure 3D as showing significantly de-enriched terms.
Figure 3C is described as both reduced and overrepresented
Minor
The results text assigns reduced mitochondrial and RNA/DNA-binding protein representation to Figure 3C, but the caption says Figure 3C shows overrepresented terms.

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Tissue-based map of the human proteome
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Background
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Autophagy in kidney homeostasis and disease
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Self-citation
Neural cell adhesion molecule 1 is a novel autoantigen in membranous lupus nephritis
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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.
Affiliations: University of Cologne (DE)
University of Freiburg (DE)
Boston Children's Hospital (US)
Mount Desert Island Biological Laboratory (US)
Corresponding author: Rinschen, Markus M.
Benzing, Thomas
Huber, Tobias B.
ORCID: Rinschen, Markus M.
Gödel, Markus
Grahammer, Florian
Zschiedrich, Stefan
Helmstädter, Martin
Kretz, Oliver
Zarei, Mostafa
Braun, Daniela A.
Dittrich, Sebastian
Daouk, Ghaleb
Schermer, Bernhard
Boerries, Melanie
Busch, Hauke
Schiffer, Mario
Bergmann, Carsten
Krüger, Marcus
Hildebrandt, Friedhelm
Benzing, Thomas
Huber, Tobias B.
Venue: Cell Reports
Publisher: Elsevier BV
Published: 2018-05
Volume: 23
Issue: 8
Pages: 2495-2508
ISSN: 2211-1247 (ISSN-L)
DOI: 10.1016/j.celrep.2018.04.059
PMC: PMC5986710
OpenAlex: W2803593737
Cited by: 105
References: 84
Citations by year: 2026: 6 · 2025: 10 · 2024: 12 · 2023: 12 · 2022: 12 · 2021: 20 · 2020: 18 · 2019: 11 · 2018: 3
FWCI: 10.66
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Locations: Cell Reports (publishedVersion, cc-by-nc-nd)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
RERO DOC (Universität Bern) (submittedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
Funders: National Institutes of Health (R01-DK076683)
Deutsche Forschungsgemeinschaft (KFO 329, Ri 2811/1-1, HU 1016/8-1, CRC 1140, HU 1016/5-1)
Bundesministerium für Bildung und Forschung (01GM1515C, FKZ 01ZX1409B, STOP-FSGS 01GM1518C)
American Society of Nephrology
Else Kröner-Fresenius-Stiftung
Fritz Thyssen Stiftung (01GM1518A, 10.16.2.026MN)
Center for Mendelian Genomics, University of Washington (U54HG006504)
European Research Council
Topics: Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Health Sciences › Medicine › Oncology › Renal and related cancers
Keywords: podocytes, glomerular disease, kidney disease, multi-omics integration, stable isotope labeling, mitochondrial translation, autophagy, cell type-specific gene expression, zebrafish knockdown, cell culture model
MeSH terms: Animals, Base Sequence, Cells, Cultured, Gene Expression Regulation, Humans, Kidney Diseases, Zebrafish, Proteome, Podocytes, Mice, Genetic Association Studies, Transcriptome

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

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