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Nuclear mechanoprotection: From tissue atlases as blueprints to distinctive regulation of nuclear lamins

Two meters of DNA in each of our cells must be protected against many types of damage. Mechanoprotection is increasingly understood to be conferred by the nuclear lamina of intermediate filament proteins, but very different patterns of expression and regulation between different cells and tissues re...

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Autores principales: Wang, Mai, Ivanovska, Irena, Vashisth, Manasvita, Discher, Dennis E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AIP Publishing LLC 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203124/
https://www.ncbi.nlm.nih.gov/pubmed/35719698
http://dx.doi.org/10.1063/5.0080392
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author Wang, Mai
Ivanovska, Irena
Vashisth, Manasvita
Discher, Dennis E.
author_facet Wang, Mai
Ivanovska, Irena
Vashisth, Manasvita
Discher, Dennis E.
author_sort Wang, Mai
collection PubMed
description Two meters of DNA in each of our cells must be protected against many types of damage. Mechanoprotection is increasingly understood to be conferred by the nuclear lamina of intermediate filament proteins, but very different patterns of expression and regulation between different cells and tissues remain a challenge to comprehend and translate into applications. We begin with a tutorial style presentation of “tissue blueprints” of lamin expression including single-cell RNA sequencing in major public datasets. Lamin-A, C profiles appear strikingly similar to those for the mechanosensitive factors Vinculin, Yap1, and Piezo1, whereas datasets for lamin-B1 align with and predict regulation by the cell cycle transcription factor, FOXM1, and further predict poor survival across multiple cancers. Various experiments support the distinction between the lamin types and add mechanistic insight into the mechano-regulation of lamin-A, C by both matrix elasticity and externally imposed tissue strain. Both A- and B-type lamins, nonetheless, protect the nucleus from rupture and damage. Ultimately, for mechanically active tissue constructs and organoids as well as cell therapies, lamin levels require particular attention as they help minimize nuclear damage and defects in a cell cycle.
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spelling pubmed-92031242022-06-17 Nuclear mechanoprotection: From tissue atlases as blueprints to distinctive regulation of nuclear lamins Wang, Mai Ivanovska, Irena Vashisth, Manasvita Discher, Dennis E. APL Bioeng Reviews Two meters of DNA in each of our cells must be protected against many types of damage. Mechanoprotection is increasingly understood to be conferred by the nuclear lamina of intermediate filament proteins, but very different patterns of expression and regulation between different cells and tissues remain a challenge to comprehend and translate into applications. We begin with a tutorial style presentation of “tissue blueprints” of lamin expression including single-cell RNA sequencing in major public datasets. Lamin-A, C profiles appear strikingly similar to those for the mechanosensitive factors Vinculin, Yap1, and Piezo1, whereas datasets for lamin-B1 align with and predict regulation by the cell cycle transcription factor, FOXM1, and further predict poor survival across multiple cancers. Various experiments support the distinction between the lamin types and add mechanistic insight into the mechano-regulation of lamin-A, C by both matrix elasticity and externally imposed tissue strain. Both A- and B-type lamins, nonetheless, protect the nucleus from rupture and damage. Ultimately, for mechanically active tissue constructs and organoids as well as cell therapies, lamin levels require particular attention as they help minimize nuclear damage and defects in a cell cycle. AIP Publishing LLC 2022-06-15 /pmc/articles/PMC9203124/ /pubmed/35719698 http://dx.doi.org/10.1063/5.0080392 Text en © 2022 Author(s). https://creativecommons.org/licenses/by/4.0/All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Reviews
Wang, Mai
Ivanovska, Irena
Vashisth, Manasvita
Discher, Dennis E.
Nuclear mechanoprotection: From tissue atlases as blueprints to distinctive regulation of nuclear lamins
title Nuclear mechanoprotection: From tissue atlases as blueprints to distinctive regulation of nuclear lamins
title_full Nuclear mechanoprotection: From tissue atlases as blueprints to distinctive regulation of nuclear lamins
title_fullStr Nuclear mechanoprotection: From tissue atlases as blueprints to distinctive regulation of nuclear lamins
title_full_unstemmed Nuclear mechanoprotection: From tissue atlases as blueprints to distinctive regulation of nuclear lamins
title_short Nuclear mechanoprotection: From tissue atlases as blueprints to distinctive regulation of nuclear lamins
title_sort nuclear mechanoprotection: from tissue atlases as blueprints to distinctive regulation of nuclear lamins
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203124/
https://www.ncbi.nlm.nih.gov/pubmed/35719698
http://dx.doi.org/10.1063/5.0080392
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