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Widespread changes in transcriptome profile of human mesenchymal stem cells induced by two-dimensional nanosilicates

Two-dimensional nanomaterials, an ultrathin class of materials such as graphene, nanoclays, transition metal dichalcogenides (TMDs), and transition metal oxides (TMOs), have emerged as a new generation of materials due to their unique properties relative to macroscale counterparts. However, little i...

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Autores principales: Carrow, James K., Cross, Lauren M., Reese, Robert W., Jaiswal, Manish K., Gregory, Carl A., Kaunas, Roland, Singh, Irtisha, Gaharwar, Akhilesh K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5924886/
https://www.ncbi.nlm.nih.gov/pubmed/29643075
http://dx.doi.org/10.1073/pnas.1716164115
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author Carrow, James K.
Cross, Lauren M.
Reese, Robert W.
Jaiswal, Manish K.
Gregory, Carl A.
Kaunas, Roland
Singh, Irtisha
Gaharwar, Akhilesh K.
author_facet Carrow, James K.
Cross, Lauren M.
Reese, Robert W.
Jaiswal, Manish K.
Gregory, Carl A.
Kaunas, Roland
Singh, Irtisha
Gaharwar, Akhilesh K.
author_sort Carrow, James K.
collection PubMed
description Two-dimensional nanomaterials, an ultrathin class of materials such as graphene, nanoclays, transition metal dichalcogenides (TMDs), and transition metal oxides (TMOs), have emerged as a new generation of materials due to their unique properties relative to macroscale counterparts. However, little is known about the transcriptome dynamics following exposure to these nanomaterials. Here, we investigate the interactions of 2D nanosilicates, a layered clay, with human mesenchymal stem cells (hMSCs) at the whole-transcriptome level by high-throughput sequencing (RNA-seq). Analysis of cell–nanosilicate interactions by monitoring changes in transcriptome profile uncovered key biophysical and biochemical cellular pathways triggered by nanosilicates. A widespread alteration of genes was observed due to nanosilicate exposure as more than 4,000 genes were differentially expressed. The change in mRNA expression levels revealed clathrin-mediated endocytosis of nanosilicates. Nanosilicate attachment to the cell membrane and subsequent cellular internalization activated stress-responsive pathways such as mitogen-activated protein kinase (MAPK), which subsequently directed hMSC differentiation toward osteogenic and chondrogenic lineages. This study provides transcriptomic insight on the role of surface-mediated cellular signaling triggered by nanomaterials and enables development of nanomaterials-based therapeutics for regenerative medicine. This approach in understanding nanomaterial–cell interactions illustrates how change in transcriptomic profile can predict downstream effects following nanomaterial treatment.
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spelling pubmed-59248862018-04-30 Widespread changes in transcriptome profile of human mesenchymal stem cells induced by two-dimensional nanosilicates Carrow, James K. Cross, Lauren M. Reese, Robert W. Jaiswal, Manish K. Gregory, Carl A. Kaunas, Roland Singh, Irtisha Gaharwar, Akhilesh K. Proc Natl Acad Sci U S A PNAS Plus Two-dimensional nanomaterials, an ultrathin class of materials such as graphene, nanoclays, transition metal dichalcogenides (TMDs), and transition metal oxides (TMOs), have emerged as a new generation of materials due to their unique properties relative to macroscale counterparts. However, little is known about the transcriptome dynamics following exposure to these nanomaterials. Here, we investigate the interactions of 2D nanosilicates, a layered clay, with human mesenchymal stem cells (hMSCs) at the whole-transcriptome level by high-throughput sequencing (RNA-seq). Analysis of cell–nanosilicate interactions by monitoring changes in transcriptome profile uncovered key biophysical and biochemical cellular pathways triggered by nanosilicates. A widespread alteration of genes was observed due to nanosilicate exposure as more than 4,000 genes were differentially expressed. The change in mRNA expression levels revealed clathrin-mediated endocytosis of nanosilicates. Nanosilicate attachment to the cell membrane and subsequent cellular internalization activated stress-responsive pathways such as mitogen-activated protein kinase (MAPK), which subsequently directed hMSC differentiation toward osteogenic and chondrogenic lineages. This study provides transcriptomic insight on the role of surface-mediated cellular signaling triggered by nanomaterials and enables development of nanomaterials-based therapeutics for regenerative medicine. This approach in understanding nanomaterial–cell interactions illustrates how change in transcriptomic profile can predict downstream effects following nanomaterial treatment. National Academy of Sciences 2018-04-24 2018-04-11 /pmc/articles/PMC5924886/ /pubmed/29643075 http://dx.doi.org/10.1073/pnas.1716164115 Text en Copyright © 2018 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle PNAS Plus
Carrow, James K.
Cross, Lauren M.
Reese, Robert W.
Jaiswal, Manish K.
Gregory, Carl A.
Kaunas, Roland
Singh, Irtisha
Gaharwar, Akhilesh K.
Widespread changes in transcriptome profile of human mesenchymal stem cells induced by two-dimensional nanosilicates
title Widespread changes in transcriptome profile of human mesenchymal stem cells induced by two-dimensional nanosilicates
title_full Widespread changes in transcriptome profile of human mesenchymal stem cells induced by two-dimensional nanosilicates
title_fullStr Widespread changes in transcriptome profile of human mesenchymal stem cells induced by two-dimensional nanosilicates
title_full_unstemmed Widespread changes in transcriptome profile of human mesenchymal stem cells induced by two-dimensional nanosilicates
title_short Widespread changes in transcriptome profile of human mesenchymal stem cells induced by two-dimensional nanosilicates
title_sort widespread changes in transcriptome profile of human mesenchymal stem cells induced by two-dimensional nanosilicates
topic PNAS Plus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5924886/
https://www.ncbi.nlm.nih.gov/pubmed/29643075
http://dx.doi.org/10.1073/pnas.1716164115
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