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


Authors: Carrow, J. K.; Cross, L. M.; Reese, R. W.; Jaiswal, M. K.; Gregory, C. A.; Kaunas, R.; Singh, I.; Gaharwar, A. K.
Article Title: Widespread changes in transcriptome profile of human mesenchymal stem cells induced by two-dimensional nanosilicates
Abstract: 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. © 2018 National Academy of Sciences. All Rights Reserved.
Keywords: signal transduction; mitogen activated protein kinase; controlled study; unclassified drug; human cell; mutation; gene; gene expression; genetic variability; cell differentiation; cell lineage; messenger rna; cell membrane; mesenchymal stem cell; nanoparticle; cellular stress response; biochemistry; cell interaction; endocytosis; transcriptome; internalization; osteoblast; rna sequence; biophysics; clathrin; regenerative medicine; rna-seq; chondrocyte; high throughput sequencing; human; priority journal; article; human mesenchymal stem cells; 2d nanomaterials; nanosilicates; whole-transcriptome sequencing; nanosilicate; transition metal dichalcogenide; transition metal oxide
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 115
Issue: 17
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2018-04-24
Start Page: E3905
End Page: E3913
Language: English
DOI: 10.1073/pnas.1716164115
PROVIDER: scopus
PMCID: PMC5924886
PUBMED: 29643075
DOI/URL:
Notes: Article -- Export Date: 1 June 2018 -- Source: Scopus
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MSK Authors
  1. Irtisha Singh
    8 Singh