title: Defined three-dimensional microenvironments boost induction of pluripotency.
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.
authors.affiliation: Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV) and School of Engineering (STI), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Caiazzo
authors.affiliation: Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV) and School of Engineering (STI), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Okawa
authors.affiliation: Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV) and School of Engineering (STI), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Ranga
authors.affiliation: School of Life Sciences, Core Facility PTECH, EPFL, 1015 Lausanne, Switzerland.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Piersigilli
authors.affiliation: Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV) and School of Engineering (STI), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Tabata
authors.affiliation: Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV) and School of Engineering (STI), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.|Institute of Chemical Sciences and Engineering, School of Basic Science (SB), EPFL, 1015 Lausanne, Switzerland.
authors.forename: Matthias P
authors.identifier: http://orcid.org/0000-0002-5898-305X
authors.initials: MP
authors.lastname: Lutolf
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D060833:Cellular Microenvironment; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*