期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 111, 期 38, 页码 13805-13810出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1415330111
关键词
mechanotransduction; neuronal differentiation; YAP/TAZ; biomaterials; glycosaminoglycans
资金
- University of Wisconsin-Madison Stem Cell and Regenerative Medicine Center
- National Institutes of Health (NIH) [R01 GM49975, R01 EB007534, R01 HL093282, R21 NS081484]
- National Science Foundation (NSF) [CBET 0745563]
- NSF [2007058921]
- NIH [T32 GM008505, 5T32 GM00721535]
- University of Wisconsin-Madison Graduate Research Fellowship
Physical stimuli can act in either a synergistic or antagonistic manner to regulate cell fate decisions, but it is less clear whether insoluble signals alone can direct human pluripotent stem (hPS) cell differentiation into specialized cell types. We previously reported that stiff materials promote nuclear localization of the Yes-associated protein (YAP) transcriptional coactivator and support long-term self-renewal of hPS cells. Here, we show that even in the presence of soluble pluripotency factors, compliant substrata inhibit the nuclear localization of YAP and promote highly efficient differentiation of hPS cells into postmitotic neurons. In the absence of neurogenic factors, the effective substrata produce neurons rapidly (2 wk) and more efficiently (> 75%) than conventional differentiation methods. The neurons derived from substrate induction express mature markers and possess action potentials. The hPS differentiation observed on compliant surfaces could be recapitulated on stiff surfaces by adding small-molecule inhibitors of F-actin polymerization or by depleting YAP. These studies reveal that the matrix alone can mediate differentiation of hPS cells into a mature cell type, independent of soluble inductive factors. That mechanical cues can override soluble signals suggests that their contributions to early tissue development and lineage commitment are profound.
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