Novel 3D analysis using optical tissue clearing documents the evolution of murine rapidly progressive glomerulonephritis

Victor G. Puelles, David Fleck, Lena Ortz, Stella Papadouri, Thiago Strieder, Alexander M.C. Böhner, James W. van der Wolde, Michael Vogt, Turgay Saritas, Christoph Kuppe, Astrid Fuss, Sylvia Menzel, Barbara M. Klinkhammer, Gerhard Müller-Newen, Felix Heymann, Leon Decker, Fabian Braun, Oliver Kretz, Tobias B. Huber, Etsuo A. Susaki & 9 others Hiroki R. Ueda, Peter Boor, Jürgen Floege, Rafael Kramann, Christian Kurts, John F. Bertram, Marc Spehr, David J. Nikolic-Paterson, Marcus J. Moeller

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Recent developments in optical tissue clearing have been difficult to apply for the morphometric analysis of organs with high cellular content and small functional structures, such as the kidney. Here, we establish combinations of genetic and immuno-labelling for single cell identification, tissue clearing and subsequent de-clarification for histoimmunopathology and transmission electron microscopy. Using advanced light microscopy and computational analyses, we investigated a murine model of crescentic nephritis, an inflammatory kidney disease typified by immune-mediated damage to glomeruli leading to the formation of hypercellular lesions and the rapid loss of kidney function induced by nephrotoxic serum. Results show a graded susceptibility of the glomeruli, significant podocyte loss and capillary injury. These effects are associated with activation of parietal epithelial cells and formation of glomerular lesions that may evolve and obstruct the kidney tubule, thereby explaining the loss of kidney function. Thus, our work provides new high-throughput endpoints for the analysis of complex tissues with single-cell resolution.

Original languageEnglish
Number of pages12
JournalKidney International
DOIs
Publication statusAccepted/In press - 15 Mar 2019

Keywords

  • computational analysis
  • crescentic nephritis
  • optical clearing
  • parietal cell activation
  • podocyte loss

Cite this

Puelles, Victor G. ; Fleck, David ; Ortz, Lena ; Papadouri, Stella ; Strieder, Thiago ; Böhner, Alexander M.C. ; van der Wolde, James W. ; Vogt, Michael ; Saritas, Turgay ; Kuppe, Christoph ; Fuss, Astrid ; Menzel, Sylvia ; Klinkhammer, Barbara M. ; Müller-Newen, Gerhard ; Heymann, Felix ; Decker, Leon ; Braun, Fabian ; Kretz, Oliver ; Huber, Tobias B. ; Susaki, Etsuo A. ; Ueda, Hiroki R. ; Boor, Peter ; Floege, Jürgen ; Kramann, Rafael ; Kurts, Christian ; Bertram, John F. ; Spehr, Marc ; Nikolic-Paterson, David J. ; Moeller, Marcus J. / Novel 3D analysis using optical tissue clearing documents the evolution of murine rapidly progressive glomerulonephritis. In: Kidney International. 2019.
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title = "Novel 3D analysis using optical tissue clearing documents the evolution of murine rapidly progressive glomerulonephritis",
abstract = "Recent developments in optical tissue clearing have been difficult to apply for the morphometric analysis of organs with high cellular content and small functional structures, such as the kidney. Here, we establish combinations of genetic and immuno-labelling for single cell identification, tissue clearing and subsequent de-clarification for histoimmunopathology and transmission electron microscopy. Using advanced light microscopy and computational analyses, we investigated a murine model of crescentic nephritis, an inflammatory kidney disease typified by immune-mediated damage to glomeruli leading to the formation of hypercellular lesions and the rapid loss of kidney function induced by nephrotoxic serum. Results show a graded susceptibility of the glomeruli, significant podocyte loss and capillary injury. These effects are associated with activation of parietal epithelial cells and formation of glomerular lesions that may evolve and obstruct the kidney tubule, thereby explaining the loss of kidney function. Thus, our work provides new high-throughput endpoints for the analysis of complex tissues with single-cell resolution.",
keywords = "computational analysis, crescentic nephritis, optical clearing, parietal cell activation, podocyte loss",
author = "Puelles, {Victor G.} and David Fleck and Lena Ortz and Stella Papadouri and Thiago Strieder and B{\"o}hner, {Alexander M.C.} and {van der Wolde}, {James W.} and Michael Vogt and Turgay Saritas and Christoph Kuppe and Astrid Fuss and Sylvia Menzel and Klinkhammer, {Barbara M.} and Gerhard M{\"u}ller-Newen and Felix Heymann and Leon Decker and Fabian Braun and Oliver Kretz and Huber, {Tobias B.} and Susaki, {Etsuo A.} and Ueda, {Hiroki R.} and Peter Boor and J{\"u}rgen Floege and Rafael Kramann and Christian Kurts and Bertram, {John F.} and Marc Spehr and Nikolic-Paterson, {David J.} and Moeller, {Marcus J.}",
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day = "15",
doi = "10.1016/j.kint.2019.02.034",
language = "English",
journal = "Kidney International",
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Puelles, VG, Fleck, D, Ortz, L, Papadouri, S, Strieder, T, Böhner, AMC, van der Wolde, JW, Vogt, M, Saritas, T, Kuppe, C, Fuss, A, Menzel, S, Klinkhammer, BM, Müller-Newen, G, Heymann, F, Decker, L, Braun, F, Kretz, O, Huber, TB, Susaki, EA, Ueda, HR, Boor, P, Floege, J, Kramann, R, Kurts, C, Bertram, JF, Spehr, M, Nikolic-Paterson, DJ & Moeller, MJ 2019, 'Novel 3D analysis using optical tissue clearing documents the evolution of murine rapidly progressive glomerulonephritis', Kidney International. https://doi.org/10.1016/j.kint.2019.02.034

Novel 3D analysis using optical tissue clearing documents the evolution of murine rapidly progressive glomerulonephritis. / Puelles, Victor G.; Fleck, David; Ortz, Lena; Papadouri, Stella; Strieder, Thiago; Böhner, Alexander M.C.; van der Wolde, James W.; Vogt, Michael; Saritas, Turgay; Kuppe, Christoph; Fuss, Astrid; Menzel, Sylvia; Klinkhammer, Barbara M.; Müller-Newen, Gerhard; Heymann, Felix; Decker, Leon; Braun, Fabian; Kretz, Oliver; Huber, Tobias B.; Susaki, Etsuo A.; Ueda, Hiroki R.; Boor, Peter; Floege, Jürgen; Kramann, Rafael; Kurts, Christian; Bertram, John F.; Spehr, Marc; Nikolic-Paterson, David J.; Moeller, Marcus J.

In: Kidney International, 15.03.2019.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Puelles, Victor G.

AU - Fleck, David

AU - Ortz, Lena

AU - Papadouri, Stella

AU - Strieder, Thiago

AU - Böhner, Alexander M.C.

AU - van der Wolde, James W.

AU - Vogt, Michael

AU - Saritas, Turgay

AU - Kuppe, Christoph

AU - Fuss, Astrid

AU - Menzel, Sylvia

AU - Klinkhammer, Barbara M.

AU - Müller-Newen, Gerhard

AU - Heymann, Felix

AU - Decker, Leon

AU - Braun, Fabian

AU - Kretz, Oliver

AU - Huber, Tobias B.

AU - Susaki, Etsuo A.

AU - Ueda, Hiroki R.

AU - Boor, Peter

AU - Floege, Jürgen

AU - Kramann, Rafael

AU - Kurts, Christian

AU - Bertram, John F.

AU - Spehr, Marc

AU - Nikolic-Paterson, David J.

AU - Moeller, Marcus J.

PY - 2019/3/15

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N2 - Recent developments in optical tissue clearing have been difficult to apply for the morphometric analysis of organs with high cellular content and small functional structures, such as the kidney. Here, we establish combinations of genetic and immuno-labelling for single cell identification, tissue clearing and subsequent de-clarification for histoimmunopathology and transmission electron microscopy. Using advanced light microscopy and computational analyses, we investigated a murine model of crescentic nephritis, an inflammatory kidney disease typified by immune-mediated damage to glomeruli leading to the formation of hypercellular lesions and the rapid loss of kidney function induced by nephrotoxic serum. Results show a graded susceptibility of the glomeruli, significant podocyte loss and capillary injury. These effects are associated with activation of parietal epithelial cells and formation of glomerular lesions that may evolve and obstruct the kidney tubule, thereby explaining the loss of kidney function. Thus, our work provides new high-throughput endpoints for the analysis of complex tissues with single-cell resolution.

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KW - crescentic nephritis

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KW - podocyte loss

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