Defined three-dimensional microenvironments boost induction of pluripotency

  • Caiazzo M
  • Okawa Y
  • Ranga A
 et al. 
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Abstract

Since the discovery of induced pluripotent stem cells (iPSCs), numerous approaches have been explored to improve the original protocol, which is based on a two-dimensional (2D) cell-culture system. Surprisingly, nothing is known about the effect of a more biologically faithful 3D environment on somatic-cell reprogramming. Here, we report a systematic analysis of how reprogramming of somatic cells occurs within engineered 3D extracellular matrices. By modulating microenvironmental stiffness, degradability and biochemical composition, we have identified a previously unknown role for biophysical effectors in the promotion of iPSC generation. We find that the physical cell confinement imposed by the 3D microenvironment boosts reprogramming through an accelerated mesenchymal-to-epithelial transition and increased epigenetic remodelling. We conclude that 3D microenvironmental signals act synergistically with reprogramming transcription factors to increase somatic plasticity.

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Authors

  • Adrian RangaHarvard Medical School

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  • Massimiliano Caiazzo

  • Yuya Okawa

  • Alessandra Piersigilli

  • Yoji Tabata

  • Matthias P. Lutolf

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