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.
Nat Mater. 2016 Mar;15(3):344-52
Caiazzo M, Okawa Y, Ranga A, Piersigilli A, Tabata Y, Lutolf MP.
The Scientist, February 22, 2018
Nature Medicine. Sept 2017; Vol 23, Nr 9: 1028-1035
Cell. 2018 Jan 11;172(1-2):373-386.
Trends Mol Med. 2017 May;23(5):393-410.
Proc Natl Acad Sci U S A. 2016 Nov 1;113(44):E6831-E6839.
Nature. 2016 Nov 24;539(7630):560-564.
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