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Cross-linked matrix rigidity and soluble retinoids synergize in nuclear lamina regulation of stem cell differentiation

Synergistic cues from extracellular matrix and soluble factors are often obscure in differentiation. Here the rigidity of cross-linked collagen synergizes with retinoids in the osteogenesis of human marrow mesenchymal stem cells (MSCs). Collagen nanofilms serve as a model matrix that MSCs can easily...

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Autores principales: Ivanovska, Irena L., Swift, Joe, Spinler, Kyle, Dingal, Dave, Cho, Sangkyun, Discher, Dennis E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541850/
https://www.ncbi.nlm.nih.gov/pubmed/28566555
http://dx.doi.org/10.1091/mbc.E17-01-0010
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author Ivanovska, Irena L.
Swift, Joe
Spinler, Kyle
Dingal, Dave
Cho, Sangkyun
Discher, Dennis E.
author_facet Ivanovska, Irena L.
Swift, Joe
Spinler, Kyle
Dingal, Dave
Cho, Sangkyun
Discher, Dennis E.
author_sort Ivanovska, Irena L.
collection PubMed
description Synergistic cues from extracellular matrix and soluble factors are often obscure in differentiation. Here the rigidity of cross-linked collagen synergizes with retinoids in the osteogenesis of human marrow mesenchymal stem cells (MSCs). Collagen nanofilms serve as a model matrix that MSCs can easily deform unless the film is enzymatically cross-linked, which promotes the spreading of cells and the stiffening of nuclei as both actomyosin assembly and nucleoskeletal lamin-A increase. Expression of lamin-A is known to be controlled by retinoic acid receptor (RAR) transcription factors, but soft matrix prevents any response to any retinoids. Rigid matrix is needed to induce rapid nuclear accumulation of the RARG isoform and for RARG-specific antagonist to increase or maintain expression of lamin-A as well as for RARG-agonist to repress expression. A progerin allele of lamin-A is regulated in the same manner in iPSC-derived MSCs. Rigid matrices are further required for eventual expression of osteogenic markers, and RARG-antagonist strongly drives lamin-A–dependent osteogenesis on rigid substrates, with pretreated xenografts calcifying in vivo to a similar extent as native bone. Proteomics-detected targets of mechanosensitive lamin-A and retinoids underscore the convergent synergy of insoluble and soluble cues in differentiation.
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spelling pubmed-55418502017-09-22 Cross-linked matrix rigidity and soluble retinoids synergize in nuclear lamina regulation of stem cell differentiation Ivanovska, Irena L. Swift, Joe Spinler, Kyle Dingal, Dave Cho, Sangkyun Discher, Dennis E. Mol Biol Cell Articles Synergistic cues from extracellular matrix and soluble factors are often obscure in differentiation. Here the rigidity of cross-linked collagen synergizes with retinoids in the osteogenesis of human marrow mesenchymal stem cells (MSCs). Collagen nanofilms serve as a model matrix that MSCs can easily deform unless the film is enzymatically cross-linked, which promotes the spreading of cells and the stiffening of nuclei as both actomyosin assembly and nucleoskeletal lamin-A increase. Expression of lamin-A is known to be controlled by retinoic acid receptor (RAR) transcription factors, but soft matrix prevents any response to any retinoids. Rigid matrix is needed to induce rapid nuclear accumulation of the RARG isoform and for RARG-specific antagonist to increase or maintain expression of lamin-A as well as for RARG-agonist to repress expression. A progerin allele of lamin-A is regulated in the same manner in iPSC-derived MSCs. Rigid matrices are further required for eventual expression of osteogenic markers, and RARG-antagonist strongly drives lamin-A–dependent osteogenesis on rigid substrates, with pretreated xenografts calcifying in vivo to a similar extent as native bone. Proteomics-detected targets of mechanosensitive lamin-A and retinoids underscore the convergent synergy of insoluble and soluble cues in differentiation. The American Society for Cell Biology 2017-07-07 /pmc/articles/PMC5541850/ /pubmed/28566555 http://dx.doi.org/10.1091/mbc.E17-01-0010 Text en © 2017 Ivanovska et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Ivanovska, Irena L.
Swift, Joe
Spinler, Kyle
Dingal, Dave
Cho, Sangkyun
Discher, Dennis E.
Cross-linked matrix rigidity and soluble retinoids synergize in nuclear lamina regulation of stem cell differentiation
title Cross-linked matrix rigidity and soluble retinoids synergize in nuclear lamina regulation of stem cell differentiation
title_full Cross-linked matrix rigidity and soluble retinoids synergize in nuclear lamina regulation of stem cell differentiation
title_fullStr Cross-linked matrix rigidity and soluble retinoids synergize in nuclear lamina regulation of stem cell differentiation
title_full_unstemmed Cross-linked matrix rigidity and soluble retinoids synergize in nuclear lamina regulation of stem cell differentiation
title_short Cross-linked matrix rigidity and soluble retinoids synergize in nuclear lamina regulation of stem cell differentiation
title_sort cross-linked matrix rigidity and soluble retinoids synergize in nuclear lamina regulation of stem cell differentiation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541850/
https://www.ncbi.nlm.nih.gov/pubmed/28566555
http://dx.doi.org/10.1091/mbc.E17-01-0010
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