Re-characterization of the Glomerulopathy in CD2AP Deficient Mice by High-Resolution Helium Ion Scanning Microscopy

Abstract Helium ion scanning microscopy (HIM) is a novel technology that directly visualizes the cell surface ultrastructure without surface coating. Despite its very high resolution, it has not been applied extensively to study biological or pathology samples. Here we report the application of this...

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Autores principales:	Kenji Tsuji, Teodor G. Păunescu, Hani Suleiman, Dongping Xie, Fahmy A. Mamuya, Jeffrey H. Miner, Hua A. Jenny Lu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7e560862969a41ccb11700805fd53622
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spelling	oai:doaj.org-article:7e560862969a41ccb11700805fd536222021-12-02T15:06:07ZRe-characterization of the Glomerulopathy in CD2AP Deficient Mice by High-Resolution Helium Ion Scanning Microscopy10.1038/s41598-017-08304-32045-2322https://doaj.org/article/7e560862969a41ccb11700805fd536222017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08304-3https://doaj.org/toc/2045-2322Abstract Helium ion scanning microscopy (HIM) is a novel technology that directly visualizes the cell surface ultrastructure without surface coating. Despite its very high resolution, it has not been applied extensively to study biological or pathology samples. Here we report the application of this powerful technology to examine the three-dimensional ultrastructural characteristics of proteinuric glomerulopathy in mice with CD2-associated protein (CD2AP) deficiency. HIM revealed the serial alteration of glomerular features including effacement and disorganization of the slit diaphragm, followed by foot process disappearance, flattening and fusion of major processes, and eventual transformation into a podocyte sheet as the disease progressed. The number and size of the filtration slit pores decreased. Strikingly, numerous “bleb” shaped microprojections were observed extending from podocyte processes and cell body, indicating significant membrane dynamics accompanying CD2AP deficiency. Visualizing the glomerular endothelium and podocyte-endothelium interface revealed the presence of endothelial damage, and disrupted podocyte and endothelial integrity in 6 week-old Cd2ap-KO mice. We used the HIM technology to investigate at nanometer scale resolution the ultrastructural alterations of the glomerular filtration apparatus in mice lacking the critical slit diaphragm-associated protein CD2AP, highlighting the great potential of HIM to provide new insights into the biology and (patho)physiology of glomerular diseases.Kenji TsujiTeodor G. PăunescuHani SuleimanDongping XieFahmy A. MamuyaJeffrey H. MinerHua A. Jenny LuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kenji Tsuji Teodor G. Păunescu Hani Suleiman Dongping Xie Fahmy A. Mamuya Jeffrey H. Miner Hua A. Jenny Lu Re-characterization of the Glomerulopathy in CD2AP Deficient Mice by High-Resolution Helium Ion Scanning Microscopy
description	Abstract Helium ion scanning microscopy (HIM) is a novel technology that directly visualizes the cell surface ultrastructure without surface coating. Despite its very high resolution, it has not been applied extensively to study biological or pathology samples. Here we report the application of this powerful technology to examine the three-dimensional ultrastructural characteristics of proteinuric glomerulopathy in mice with CD2-associated protein (CD2AP) deficiency. HIM revealed the serial alteration of glomerular features including effacement and disorganization of the slit diaphragm, followed by foot process disappearance, flattening and fusion of major processes, and eventual transformation into a podocyte sheet as the disease progressed. The number and size of the filtration slit pores decreased. Strikingly, numerous “bleb” shaped microprojections were observed extending from podocyte processes and cell body, indicating significant membrane dynamics accompanying CD2AP deficiency. Visualizing the glomerular endothelium and podocyte-endothelium interface revealed the presence of endothelial damage, and disrupted podocyte and endothelial integrity in 6 week-old Cd2ap-KO mice. We used the HIM technology to investigate at nanometer scale resolution the ultrastructural alterations of the glomerular filtration apparatus in mice lacking the critical slit diaphragm-associated protein CD2AP, highlighting the great potential of HIM to provide new insights into the biology and (patho)physiology of glomerular diseases.
format	article
author	Kenji Tsuji Teodor G. Păunescu Hani Suleiman Dongping Xie Fahmy A. Mamuya Jeffrey H. Miner Hua A. Jenny Lu
author_facet	Kenji Tsuji Teodor G. Păunescu Hani Suleiman Dongping Xie Fahmy A. Mamuya Jeffrey H. Miner Hua A. Jenny Lu
author_sort	Kenji Tsuji
title	Re-characterization of the Glomerulopathy in CD2AP Deficient Mice by High-Resolution Helium Ion Scanning Microscopy
title_short	Re-characterization of the Glomerulopathy in CD2AP Deficient Mice by High-Resolution Helium Ion Scanning Microscopy
title_full	Re-characterization of the Glomerulopathy in CD2AP Deficient Mice by High-Resolution Helium Ion Scanning Microscopy
title_fullStr	Re-characterization of the Glomerulopathy in CD2AP Deficient Mice by High-Resolution Helium Ion Scanning Microscopy
title_full_unstemmed	Re-characterization of the Glomerulopathy in CD2AP Deficient Mice by High-Resolution Helium Ion Scanning Microscopy
title_sort	re-characterization of the glomerulopathy in cd2ap deficient mice by high-resolution helium ion scanning microscopy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/7e560862969a41ccb11700805fd53622
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Re-characterization of the Glomerulopathy in CD2AP Deficient Mice by High-Resolution Helium Ion Scanning Microscopy

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