Single cell imaging-based chromatin biomarkers for tumor progression

Abstract Tumour progression within the tissue microenvironment is accompanied by complex biomechanical alterations of the extracellular environment. While histopathology images provide robust biochemical markers for tumor progression in clinical settings, a quantitative single cell score using nucle...

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Autores principales:	Saradha Venkatachalapathy, Doorgesh S. Jokhun, Madhavi Andhari, G. V. Shivashankar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/187404ec50c1466fa9f6444f512aaf75
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spelling	oai:doaj.org-article:187404ec50c1466fa9f6444f512aaf752021-12-05T12:15:08ZSingle cell imaging-based chromatin biomarkers for tumor progression10.1038/s41598-021-02441-62045-2322https://doaj.org/article/187404ec50c1466fa9f6444f512aaf752021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02441-6https://doaj.org/toc/2045-2322Abstract Tumour progression within the tissue microenvironment is accompanied by complex biomechanical alterations of the extracellular environment. While histopathology images provide robust biochemical markers for tumor progression in clinical settings, a quantitative single cell score using nuclear morphology and chromatin organization integrated with the long range mechanical coupling within the tumor microenvironment is missing. We propose that the spatial chromatin organization in individual nuclei characterises the cell state and their alterations during tumor progression. In this paper, we first built an image analysis pipeline and implemented it to classify nuclei from patient derived breast tissue biopsies of various cancer stages based on their nuclear and chromatin features. Replacing H&E with DNA binding dyes such as Hoescht stained tissue biopsies, we improved the classification accuracy. Using the nuclear morphology and chromatin organization features, we constructed a pseudo-time model to identify the chromatin state changes that occur during tumour progression. This enabled us to build a single-cell mechano-genomic score that characterises the cell state during tumor progression from a normal to a metastatic state. To gain further insights into the alterations in the local tissue microenvironments, we also used the nuclear orientations to identify spatial neighbourhoods that have been posited to drive tumor progression. Collectively, we demonstrate that image-based single cell chromatin and nuclear features are important single cell biomarkers for phenotypic mapping of tumor progression.Saradha VenkatachalapathyDoorgesh S. JokhunMadhavi AndhariG. V. ShivashankarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Saradha Venkatachalapathy Doorgesh S. Jokhun Madhavi Andhari G. V. Shivashankar Single cell imaging-based chromatin biomarkers for tumor progression
description	Abstract Tumour progression within the tissue microenvironment is accompanied by complex biomechanical alterations of the extracellular environment. While histopathology images provide robust biochemical markers for tumor progression in clinical settings, a quantitative single cell score using nuclear morphology and chromatin organization integrated with the long range mechanical coupling within the tumor microenvironment is missing. We propose that the spatial chromatin organization in individual nuclei characterises the cell state and their alterations during tumor progression. In this paper, we first built an image analysis pipeline and implemented it to classify nuclei from patient derived breast tissue biopsies of various cancer stages based on their nuclear and chromatin features. Replacing H&E with DNA binding dyes such as Hoescht stained tissue biopsies, we improved the classification accuracy. Using the nuclear morphology and chromatin organization features, we constructed a pseudo-time model to identify the chromatin state changes that occur during tumour progression. This enabled us to build a single-cell mechano-genomic score that characterises the cell state during tumor progression from a normal to a metastatic state. To gain further insights into the alterations in the local tissue microenvironments, we also used the nuclear orientations to identify spatial neighbourhoods that have been posited to drive tumor progression. Collectively, we demonstrate that image-based single cell chromatin and nuclear features are important single cell biomarkers for phenotypic mapping of tumor progression.
format	article
author	Saradha Venkatachalapathy Doorgesh S. Jokhun Madhavi Andhari G. V. Shivashankar
author_facet	Saradha Venkatachalapathy Doorgesh S. Jokhun Madhavi Andhari G. V. Shivashankar
author_sort	Saradha Venkatachalapathy
title	Single cell imaging-based chromatin biomarkers for tumor progression
title_short	Single cell imaging-based chromatin biomarkers for tumor progression
title_full	Single cell imaging-based chromatin biomarkers for tumor progression
title_fullStr	Single cell imaging-based chromatin biomarkers for tumor progression
title_full_unstemmed	Single cell imaging-based chromatin biomarkers for tumor progression
title_sort	single cell imaging-based chromatin biomarkers for tumor progression
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/187404ec50c1466fa9f6444f512aaf75
work_keys_str_mv	AT saradhavenkatachalapathy singlecellimagingbasedchromatinbiomarkersfortumorprogression AT doorgeshsjokhun singlecellimagingbasedchromatinbiomarkersfortumorprogression AT madhaviandhari singlecellimagingbasedchromatinbiomarkersfortumorprogression AT gvshivashankar singlecellimagingbasedchromatinbiomarkersfortumorprogression
_version_	1718372119044161536

Single cell imaging-based chromatin biomarkers for tumor progression

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