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.
Original language | English |
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Pages (from-to) | 344-52 |
Number of pages | 9 |
Journal | Nature Materials |
Volume | 15 |
Issue number | 3 |
DOIs | |
Publication status | Published - 11 Jan 2016 |
Keywords
- Animals
- Cell Culture Techniques
- Cell Differentiation
- Cellular Microenvironment
- Epithelial Cells
- Gene Expression Regulation
- Humans
- Materials Testing
- Mesenchymal Stromal Cells
- Mice
- Pluripotent Stem Cells
- Journal Article
- Research Support, Non-U.S. Gov't