期刊
BIOMATERIALS
卷 50, 期 -, 页码 87-97出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2015.01.019
关键词
Human pluripotent stem cells; Micropatterning; Mechanical forces; Cell fate heterogeneity
资金
- Institute of Bioengineering and Nanotechnology, Biomedical Research Council, Agency for Science, Technology and Research (A*STAR) of Singapore
- Jassen Cilag Singapore, Singapore-MIT Alliance for Research and Technology BioSyM and Mechanobiology Institute (MBI) [R714-006-008]
Heterogeneity in human pluripotent stem cell (PSC) fates is partially caused by mechanical asymmetry arising from spatial polarization of cell cell and cell-matrix adhesions. Independent studies have shown that integrin and E-cadherin adhesions promote opposing differentiation and pluripotent fates respectively although their crosstalk mechanism in modulating cell fate heterogeneity remains unknown. Here, we demonstrated that spatial polarization of integrin and E-cadherin adhesions in a human PSC colony compete to recruit Rho-ROCK activated myosin II to different localities to pattern pluripotent-differentiation decisions, resulting in spatially heterogeneous colonies. Cell micropatterning was used to modulate the spatial polarization of cell adhesions, which enabled us to prospectively determine localization patterns of activated myosin II and mesoendoderm differentiation. Direct inhibition of Rho-ROCK-myosin II activation phenocopied E-cadherin rather than integrin inhibition to form uniformly differentiated colonies. This indicated that E-cadherin was the primary gatekeeper to differentiation progression. This insight allows for biomaterials to be tailored for human PSC maintenance or differentiation with minimal heterogeneity. (C) 2015 Elsevier Ltd. All rights reserved.
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