MOLECULAR REGULATION OF CELLULAR INTERACTIONS BY THE RHO-ROCK-MYOSIN II SIGNALING AXIS IN PLURIPOTENT STEM CELLS

Abstract

Pluripotent stem (PS) cells have the ability to replicate themselves (self-renew) and to generate virtually any given cell type in the adult body (pluripotency). Human PS (hPS) cells are therefore considered promising sources for future cell replacement therapy. Embryonic stem (ES) cells are the major type of PS cells that are derived from blastocyst embryos. Germ cells from testis can also become PS cells when cultured for a long period with a combination of growth factors. Alternatively, differentiated somatic cells can also be converted to PS cells by the method called nuclear reprogramming. This includes somatic cell nuclear transfer where a somatic cell nucleus is injected into an enucleated oocyte giving rise to a reprogrammed PS cell, as well as the recently developed technique of reprogramming differentiated somatic cells into induced pluripotent stem (iPS) cells by introducing defined transcription factors. Regardless of the sources and generation methods, PS cells share common epithelial structures and maintain tight cellular interactions. Although the molecular mechanisms that regulate self-renewal and pluripotency of PS cells have been extensively studied, the basic cellular interactions that govern how PS cells control cell-cell and cell-matrix adhesions are still not fully understood. In addition, there are several obstacles in the current culture methods for hPS cells that need to be overcome in order to achieve the highest safety and consistency required for clinical applications. A Rho-mediated signaling axis has recently been determined to be the core machinery that integrates cellular interactions between PS cells. By chemically engineering this axis, hPS cells are able to self-renew under completely defined conditions while maintaining their multi-differentiation capacities. When combined with the rapid progress in research focusing on iPS cells, these studies on cell-cell and cell-matrix adhesion in PS cells may not only contribute to further understanding PS cell biology, but also lead to the development of novel technologies enabling the derivation and growth of clinically relevant hPS cells for regenerative therapies.