51. The nuclear import of the transcription factor MyoD is reduced in mesenchymal stem cells grown in a 3D micro-engineered niche.
- Author
-
Jacchetti E, Nasehi R, Boeri L, Parodi V, Negro A, Albani D, Osellame R, Cerullo G, Matas JFR, and Raimondi MT
- Subjects
- Cell Differentiation genetics, Cell Nucleus metabolism, Cells, Cultured, Gene Expression Regulation, Humans, Nuclear Envelope genetics, Nuclear Envelope metabolism, Nuclear Pore genetics, Stem Cell Niche genetics, Active Transport, Cell Nucleus genetics, Cell Nucleus genetics, Mesenchymal Stem Cells metabolism, MyoD Protein genetics
- Abstract
Smart biomaterials are increasingly being used to control stem cell fate in vitro by the recapitulation of the native niche microenvironment. By integrating experimental measurements with numerical models, we show that in mesenchymal stem cells grown inside a 3D synthetic niche both nuclear transport of a myogenic factor and the passive nuclear diffusion of a smaller inert protein are reduced. Our results also suggest that cell morphology modulates nuclear proteins import through a partition of the nuclear envelope surface, which is a thin but extremely permeable annular portion in cells cultured on 2D substrates. Therefore, our results support the hypothesis that in stem cell differentiation, the nuclear import of gene-regulating transcription factors is controlled by a strain-dependent nuclear envelope permeability, probably related to the reorganization of stretch-activated nuclear pore complexes.
- Published
- 2021
- Full Text
- View/download PDF