Substratum-induced differentiation of human pluripotent stem cells reveals the coactivator YAP is a potent regulator of neuronal specification.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Musah, S; Wrighton, PJ; Zaltsman, Y; Zhong, X; Zorn, S; Parlato, MB; Hsiao, C; Palecek, SP; Chang, Q; Murphy, WL; Kiessling, LL
Published Date
- September 8, 2014
Published In
Volume / Issue
- 111 / 38
Start / End Page
- 13805 - 13810
PubMed ID
- 25201954
Pubmed Central ID
- PMC4183276
Electronic International Standard Serial Number (EISSN)
- 1091-6490
International Standard Serial Number (ISSN)
- 0027-8424
Digital Object Identifier (DOI)
- 10.1073/pnas.1415330111
Language
- eng