Geometrically defined environments direct cell division rate and subcellular YAP localization in single mouse embryonic stem cells

Abstract Mechanotransduction via yes-associated protein (YAP) is a central mechanism for decision-making in mouse embryonic stem cells (mESCs). Nuclear localization of YAP is tightly connected to pluripotency and increases the cell division rate (CDR). How the geometry of the extracellular environme...

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Autores principales:	Sarah Bertels, Mona Jaggy, Benjamin Richter, Stephan Keppler, Kerstin Weber, Elisa Genthner, Andrea C. Fischer, Michael Thiel, Martin Wegener, Alexandra M. Greiner, Tatjana J. Autenrieth, Martin Bastmeyer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/80ffe03679444a2aa6e0e27b7e0d2b1e
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spelling	oai:doaj.org-article:80ffe03679444a2aa6e0e27b7e0d2b1e2021-12-02T13:41:00ZGeometrically defined environments direct cell division rate and subcellular YAP localization in single mouse embryonic stem cells10.1038/s41598-021-88336-y2045-2322https://doaj.org/article/80ffe03679444a2aa6e0e27b7e0d2b1e2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88336-yhttps://doaj.org/toc/2045-2322Abstract Mechanotransduction via yes-associated protein (YAP) is a central mechanism for decision-making in mouse embryonic stem cells (mESCs). Nuclear localization of YAP is tightly connected to pluripotency and increases the cell division rate (CDR). How the geometry of the extracellular environment influences mechanotransduction, thereby YAP localization, and decision-making of single isolated mESCs is largely unknown. To investigate this relation, we produced well-defined 2D and 2.5D microenvironments and monitored CDR and subcellular YAP localization in single mESCs hence excluding cell–cell interactions. By systematically varying size and shape of the 2D and 2.5D substrates we observed that the geometry of the growth environment affects the CDR. Whereas CDR increases with increasing adhesive area in 2D, CDR is highest in small 2.5D micro-wells. Here, mESCs attach to all four walls and exhibit a cross-shaped cell and nuclear morphology. This observation indicates that changes in cell shape are linked to a high CDR. Inhibition of actomyosin activity abrogate these effects. Correspondingly, nuclear YAP localization decreases in inhibitor treated cells, suggesting a relation between cell shape, intracellular forces, and cell division rate. The simplicity of our system guarantees high standardization and reproducibility for monitoring stem cell reactions and allows addressing a variety of fundamental biological questions on a single cell level.Sarah BertelsMona JaggyBenjamin RichterStephan KepplerKerstin WeberElisa GenthnerAndrea C. FischerMichael ThielMartin WegenerAlexandra M. GreinerTatjana J. AutenriethMartin BastmeyerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sarah Bertels Mona Jaggy Benjamin Richter Stephan Keppler Kerstin Weber Elisa Genthner Andrea C. Fischer Michael Thiel Martin Wegener Alexandra M. Greiner Tatjana J. Autenrieth Martin Bastmeyer Geometrically defined environments direct cell division rate and subcellular YAP localization in single mouse embryonic stem cells
description	Abstract Mechanotransduction via yes-associated protein (YAP) is a central mechanism for decision-making in mouse embryonic stem cells (mESCs). Nuclear localization of YAP is tightly connected to pluripotency and increases the cell division rate (CDR). How the geometry of the extracellular environment influences mechanotransduction, thereby YAP localization, and decision-making of single isolated mESCs is largely unknown. To investigate this relation, we produced well-defined 2D and 2.5D microenvironments and monitored CDR and subcellular YAP localization in single mESCs hence excluding cell–cell interactions. By systematically varying size and shape of the 2D and 2.5D substrates we observed that the geometry of the growth environment affects the CDR. Whereas CDR increases with increasing adhesive area in 2D, CDR is highest in small 2.5D micro-wells. Here, mESCs attach to all four walls and exhibit a cross-shaped cell and nuclear morphology. This observation indicates that changes in cell shape are linked to a high CDR. Inhibition of actomyosin activity abrogate these effects. Correspondingly, nuclear YAP localization decreases in inhibitor treated cells, suggesting a relation between cell shape, intracellular forces, and cell division rate. The simplicity of our system guarantees high standardization and reproducibility for monitoring stem cell reactions and allows addressing a variety of fundamental biological questions on a single cell level.
format	article
author	Sarah Bertels Mona Jaggy Benjamin Richter Stephan Keppler Kerstin Weber Elisa Genthner Andrea C. Fischer Michael Thiel Martin Wegener Alexandra M. Greiner Tatjana J. Autenrieth Martin Bastmeyer
author_facet	Sarah Bertels Mona Jaggy Benjamin Richter Stephan Keppler Kerstin Weber Elisa Genthner Andrea C. Fischer Michael Thiel Martin Wegener Alexandra M. Greiner Tatjana J. Autenrieth Martin Bastmeyer
author_sort	Sarah Bertels
title	Geometrically defined environments direct cell division rate and subcellular YAP localization in single mouse embryonic stem cells
title_short	Geometrically defined environments direct cell division rate and subcellular YAP localization in single mouse embryonic stem cells
title_full	Geometrically defined environments direct cell division rate and subcellular YAP localization in single mouse embryonic stem cells
title_fullStr	Geometrically defined environments direct cell division rate and subcellular YAP localization in single mouse embryonic stem cells
title_full_unstemmed	Geometrically defined environments direct cell division rate and subcellular YAP localization in single mouse embryonic stem cells
title_sort	geometrically defined environments direct cell division rate and subcellular yap localization in single mouse embryonic stem cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/80ffe03679444a2aa6e0e27b7e0d2b1e
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Geometrically defined environments direct cell division rate and subcellular YAP localization in single mouse embryonic stem cells

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