Article,

Actomyosin contractility plays a role in \MAP2\ expression during nanotopography-directed neuronal differentiation of human embryonic stem cells

, , and .
Biomaterials, 47 (0): 20--28 (2015)
DOI: http://dx.doi.org/10.1016/j.biomaterials.2015.01.003

Abstract

Abstract Pluripotent human embryonic stem cells (hESCs) have the capability of differentiating into different lineages based on specific environmental cues. We had previously shown that hESCs can be primed to differentiate into either neurons or glial cells, depending on the arrangement, geometry and size of their substrate topography. In particular, anisotropically patterned substrates like gratings were found to favour the differentiation of hESCs into neurons rather than glial cells. In this study, our aim is to elucidate the underlying mechanisms of topography-induced differentiation of hESCs towards neuronal lineages. We show that high actomyosin contractility induced by a nano-grating topography is crucial for neuronal maturation. Treatment of cells with the myosin \II\ inhibitor (blebbistatin) and myosin light chain kinase inhibitor (ML-7) greatly reduces the expression level of microtubule-associated protein 2 (MAP2). On the other hand, our qPCR array results showed that PAX5, \BRN3A\ and \NEUROD1\ were highly expressed in hESCs grown on nano-grating substrates as compared to unpatterned substrates, suggesting the possible involvement of these genes in topography-mediated neuronal differentiation of hESCs. Interestingly, \YAP\ was localized to the cytoplasm of differentiating hESCs. Taken together, our study has provided new insights in understanding the mechanotransduction of topographical cues during neuronal differentiation of hESCs.

Tags

Users

  • @bkoch

Comments and Reviews