Quantitative super-resolution microscopy reveals the differences in the nanoscale distribution of nuclear phosphatidylinositol 4,5-bisphosphate in human healthy skin and skin warts

Introduction: Imaging of human clinical formalin-fixed paraffin-embedded (FFPE) tissue sections provides insights into healthy and diseased states and therefore represents a valuable resource for basic research, as well as for diagnostic and clinical purposes. However, conventional light microscopy...

Full description

Bibliographic Details
Main Authors: Peter Hoboth, Martin Sztacho, Alexander Quaas, Baki Akgül, Pavel Hozák
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-07-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2023.1217637/full
_version_ 1797785234700238848
author Peter Hoboth
Martin Sztacho
Alexander Quaas
Baki Akgül
Pavel Hozák
Pavel Hozák
author_facet Peter Hoboth
Martin Sztacho
Alexander Quaas
Baki Akgül
Pavel Hozák
Pavel Hozák
author_sort Peter Hoboth
collection DOAJ
description Introduction: Imaging of human clinical formalin-fixed paraffin-embedded (FFPE) tissue sections provides insights into healthy and diseased states and therefore represents a valuable resource for basic research, as well as for diagnostic and clinical purposes. However, conventional light microscopy does not allow to observe the molecular details of tissue and cell architecture due to the diffraction limit of light. Super-resolution microscopy overcomes this limitation and provides access to the nanoscale details of tissue and cell organization.Methods: Here, we used quantitative multicolor stimulated emission depletion (STED) nanoscopy to study the nanoscale distribution of the nuclear phosphatidylinositol 4,5-bisphosphate (nPI(4,5)P2) with respect to the nuclear speckles (NS) marker SON.Results: Increased nPI(4,5)P2 signals were previously linked to human papillomavirus (HPV)-mediated carcinogenesis, while NS-associated PI(4,5)P2 represents the largest pool of nPI(4,5)P2 visualized by staining and microscopy. The implementation of multicolor STED nanoscopy in human clinical FFPE skin and wart sections allowed us to provide here the quantitative evidence for higher levels of NS-associated PI(4,5)P2 in HPV-induced warts compared to control skin.Discussion: These data expand the previous reports of HPV-induced increase of nPI(4,5)P2 levels and reveal for the first time the functional, tissue-specific localization of nPI(4,5)P2 within NS in clinically relevant samples. Moreover, our approach is widely applicable to other human clinical FFPE tissues as an informative addition to the classical histochemistry.
first_indexed 2024-03-13T00:51:12Z
format Article
id doaj.art-5508c7f721834762a759861ee4f41d39
institution Directory Open Access Journal
issn 2296-634X
language English
last_indexed 2024-03-13T00:51:12Z
publishDate 2023-07-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Cell and Developmental Biology
spelling doaj.art-5508c7f721834762a759861ee4f41d392023-07-07T13:54:28ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-07-011110.3389/fcell.2023.12176371217637Quantitative super-resolution microscopy reveals the differences in the nanoscale distribution of nuclear phosphatidylinositol 4,5-bisphosphate in human healthy skin and skin wartsPeter Hoboth0Martin Sztacho1Alexander Quaas2Baki Akgül3Pavel Hozák4Pavel Hozák5Department of Biology of the Cell Nucleus, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, CzechiaDepartment of Biology of the Cell Nucleus, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, CzechiaInstitute of Pathology, Medical Faculty and University Hospital Cologne, Cologne, GermanyInstitute of Virology, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, GermanyDepartment of Biology of the Cell Nucleus, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, CzechiaMicroscopy Centre, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, CzechiaIntroduction: Imaging of human clinical formalin-fixed paraffin-embedded (FFPE) tissue sections provides insights into healthy and diseased states and therefore represents a valuable resource for basic research, as well as for diagnostic and clinical purposes. However, conventional light microscopy does not allow to observe the molecular details of tissue and cell architecture due to the diffraction limit of light. Super-resolution microscopy overcomes this limitation and provides access to the nanoscale details of tissue and cell organization.Methods: Here, we used quantitative multicolor stimulated emission depletion (STED) nanoscopy to study the nanoscale distribution of the nuclear phosphatidylinositol 4,5-bisphosphate (nPI(4,5)P2) with respect to the nuclear speckles (NS) marker SON.Results: Increased nPI(4,5)P2 signals were previously linked to human papillomavirus (HPV)-mediated carcinogenesis, while NS-associated PI(4,5)P2 represents the largest pool of nPI(4,5)P2 visualized by staining and microscopy. The implementation of multicolor STED nanoscopy in human clinical FFPE skin and wart sections allowed us to provide here the quantitative evidence for higher levels of NS-associated PI(4,5)P2 in HPV-induced warts compared to control skin.Discussion: These data expand the previous reports of HPV-induced increase of nPI(4,5)P2 levels and reveal for the first time the functional, tissue-specific localization of nPI(4,5)P2 within NS in clinically relevant samples. Moreover, our approach is widely applicable to other human clinical FFPE tissues as an informative addition to the classical histochemistry.https://www.frontiersin.org/articles/10.3389/fcell.2023.1217637/fullformalin-fixed paraffin-embedded tissue sectionsSTED nanoscopycell nucleushuman papillomavirus (HPV)nuclear architecturephosphatidylinositol 4,5-bisphosphate
spellingShingle Peter Hoboth
Martin Sztacho
Alexander Quaas
Baki Akgül
Pavel Hozák
Pavel Hozák
Quantitative super-resolution microscopy reveals the differences in the nanoscale distribution of nuclear phosphatidylinositol 4,5-bisphosphate in human healthy skin and skin warts
Frontiers in Cell and Developmental Biology
formalin-fixed paraffin-embedded tissue sections
STED nanoscopy
cell nucleus
human papillomavirus (HPV)
nuclear architecture
phosphatidylinositol 4,5-bisphosphate
title Quantitative super-resolution microscopy reveals the differences in the nanoscale distribution of nuclear phosphatidylinositol 4,5-bisphosphate in human healthy skin and skin warts
title_full Quantitative super-resolution microscopy reveals the differences in the nanoscale distribution of nuclear phosphatidylinositol 4,5-bisphosphate in human healthy skin and skin warts
title_fullStr Quantitative super-resolution microscopy reveals the differences in the nanoscale distribution of nuclear phosphatidylinositol 4,5-bisphosphate in human healthy skin and skin warts
title_full_unstemmed Quantitative super-resolution microscopy reveals the differences in the nanoscale distribution of nuclear phosphatidylinositol 4,5-bisphosphate in human healthy skin and skin warts
title_short Quantitative super-resolution microscopy reveals the differences in the nanoscale distribution of nuclear phosphatidylinositol 4,5-bisphosphate in human healthy skin and skin warts
title_sort quantitative super resolution microscopy reveals the differences in the nanoscale distribution of nuclear phosphatidylinositol 4 5 bisphosphate in human healthy skin and skin warts
topic formalin-fixed paraffin-embedded tissue sections
STED nanoscopy
cell nucleus
human papillomavirus (HPV)
nuclear architecture
phosphatidylinositol 4,5-bisphosphate
url https://www.frontiersin.org/articles/10.3389/fcell.2023.1217637/full
work_keys_str_mv AT peterhoboth quantitativesuperresolutionmicroscopyrevealsthedifferencesinthenanoscaledistributionofnuclearphosphatidylinositol45bisphosphateinhumanhealthyskinandskinwarts
AT martinsztacho quantitativesuperresolutionmicroscopyrevealsthedifferencesinthenanoscaledistributionofnuclearphosphatidylinositol45bisphosphateinhumanhealthyskinandskinwarts
AT alexanderquaas quantitativesuperresolutionmicroscopyrevealsthedifferencesinthenanoscaledistributionofnuclearphosphatidylinositol45bisphosphateinhumanhealthyskinandskinwarts
AT bakiakgul quantitativesuperresolutionmicroscopyrevealsthedifferencesinthenanoscaledistributionofnuclearphosphatidylinositol45bisphosphateinhumanhealthyskinandskinwarts
AT pavelhozak quantitativesuperresolutionmicroscopyrevealsthedifferencesinthenanoscaledistributionofnuclearphosphatidylinositol45bisphosphateinhumanhealthyskinandskinwarts
AT pavelhozak quantitativesuperresolutionmicroscopyrevealsthedifferencesinthenanoscaledistributionofnuclearphosphatidylinositol45bisphosphateinhumanhealthyskinandskinwarts