Defined three-dimensional microenvironments boost induction of pluripotency.
Nat Mater
; 15(3): 344-52, 2016 Mar.
Article
em En
| MEDLINE
| ID: mdl-26752655
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
/
Técnicas de Cultura de Células
/
Células-Tronco Pluripotentes
/
Células Epiteliais
/
Células-Tronco Mesenquimais
/
Microambiente Celular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Mater
Assunto da revista:
CIENCIA
/
QUIMICA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Suíça