Modulation of integrin and E-cadherin-mediated adhesions to spatially control heterogeneity in human pluripotent stem cell differentiation

Biomaterials
Yi-Chin TohHanry Yu

Abstract

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 heterogene...Continue Reading

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Citations

Sep 10, 2015·Stem Cells·Naresh PolisettiUrsula Schlötzer-Schrehardt
Oct 5, 2017·Biofabrication·Elise DeSimoneThomas Scheibel
Feb 28, 2016·Journal of Cell Science·Keeley L MuiRichard K Assoian
Jan 11, 2017·Tissue Engineering. Part C, Methods·Mark C AllenbyAthanasios Mantalaris
Apr 25, 2019·Scientific Reports·Mary C RegierKelly R Stevens
Nov 11, 2015·Journal of Nanobiotechnology·Udesh DhawanWen-Liang Chen
Mar 25, 2019·Stem Cells International·Rosaria SantoroGiulio Pompilio

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