Article | Published:

Biophysical regulation of epigenetic state and cell reprogramming

Nature Materials volume 12, pages 11541162 (2013) | Download Citation

Abstract

Biochemical factors can help reprogram somatic cells into pluripotent stem cells, yet the role of biophysical factors during reprogramming is unknown. Here, we show that biophysical cues, in the form of parallel microgrooves on the surface of cell-adhesive substrates, can replace the effects of small-molecule epigenetic modifiers and significantly improve reprogramming efficiency. The mechanism relies on the mechanomodulation of the cells’ epigenetic state. Specifically, decreased histone deacetylase activity and upregulation of the expression of WD repeat domain 5 (WDR5)—a subunit of H3 methyltranferase—by microgrooved surfaces lead to increased histone H3 acetylation and methylation. We also show that microtopography promotes a mesenchymal-to-epithelial transition in adult fibroblasts. Nanofibrous scaffolds with aligned fibre orientation produce effects similar to those produced by microgrooves, suggesting that changes in cell morphology may be responsible for modulation of the epigenetic state. These findings have important implications in cell biology and in the optimization of biomaterials for cell-engineering applications.

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Acknowledgements

This work is supported in part by grants from the California Institute of Regenerative Medicine (RB3-05232) and the National Institute of Health (EB012240; to S.L.), fellowships from the Ford Foundation and Siebel Scholars Foundation (to T.L.D.), a fellowship from the National Science Foundation GRFP (to J.S.), and the Fulbright-France Commission (to T.H.). The authors would like to thank M. West at the CIRM/QB3 Shared Stem Cell Facility of UC Berkeley, I. Conboy, D. Wang, C. Elabd, T. Yamaguchi, C. W. Huang, I. Grubisic, W. C. Huang, E. Su, A. Chang and J. Zhang for their assistance and fruitful discussions. The pLOVE 302/367 plasmid was provided by the laboratory of R. Blelloch.

Author information

Author notes

    • Constant Morez
    •  & Timothee Houssin

    These authors contributed equally to this work

Affiliations

  1. UC Berkeley & UCSF Joint Graduate Program in Bioengineering, Berkeley/San Francisco, California 94720/94143, USA

    • Timothy L. Downing
    • , Jennifer Soto
    • , David V. Schaffer
    •  & Song Li
  2. Department of Bioengineering, University of California, Berkeley, B108A Stanley Hall, Berkeley, California 94720-1762, USA

    • Timothy L. Downing
    • , Jennifer Soto
    • , Constant Morez
    • , Timothee Houssin
    • , Falei Yuan
    • , Julia Chu
    • , Shyam Patel
    • , David V. Schaffer
    •  & Song Li
  3. Ecole Polytechnique, 91128 Palaiseau, France

    • Constant Morez
  4. University Lille Nord de France, F-59000 Lille, France

    • Timothee Houssin
  5. Department of Chemical and Biomolecular Engineering, University of California, Berkeley, California 94720-1762, USA

    • Ashley Fritz
    •  & David V. Schaffer
  6. Med-X Center, Shanghai Jiao Tong University, Shanghai 200030, China

    • Falei Yuan

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Contributions

S.L., T.L.D., J.S., C.M., T.H. and D.V.S. designed the experiments. T.L.D., J.S., C.M., T.H., F.Y., J.C., A.F. and S.P. carried out experiments and analysed the data. S.L., T.L.D. and J.S. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Song Li.

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DOI

https://doi.org/10.1038/nmat3777