Cargando…
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...
Autores principales: | , , , |
---|---|
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 |
_version_ | 1784728659994607616 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9203124 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | AIP Publishing LLC |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT wangmai nuclearmechanoprotectionfromtissueatlasesasblueprintstodistinctiveregulationofnuclearlamins AT ivanovskairena nuclearmechanoprotectionfromtissueatlasesasblueprintstodistinctiveregulationofnuclearlamins AT vashisthmanasvita nuclearmechanoprotectionfromtissueatlasesasblueprintstodistinctiveregulationofnuclearlamins AT discherdennise nuclearmechanoprotectionfromtissueatlasesasblueprintstodistinctiveregulationofnuclearlamins |