Regulation and mechanism of YAP/TAZ in the mechanical microenvironment of stem cells (Review)

Abstract

Stem cells receive cues from their physical and mechanical microenvironment via mechanosensing and mechanotransduction. These cues affect proliferation, self-renewal and differentiation into specific cell fates. A growing body of evidence suggests that yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) mechanotransduction is key for driving stem cell behavior and regeneration via the Hippo and other signaling pathways. YAP/TAZ receive a range of physical cues, including extracellular matrix stiffness, cell geometry, flow shear stress and mechanical forces in the cytoskeleton, and translate them into cell-specific transcriptional programs. However, the mechanism by which mechanical signals regulate YAP/TAZ activity in stem cells is not fully understand. The present review summarizes the current knowledge of the mechanisms involved in YAP/TAZ regulation on the physical and mechanical microenvironment, as well as its potential effects on stem cell differentiation. Contents 1. Introduction 2. Regulation of YAP/TAZ in mechanotransduction in stem cells 3. Mechanism of YAP/TAZ regulation 4. Conclusion

Role of YAP as a Mechanosensing Molecule in Stem Cells and Stem Cell-Derived Hematopoietic Cells

“…The upstream regulators of YAP related to mechanical forces in PSCs, including substrate stiffness [ 105 ] and surface topography [ 106 ], have been studied recently. The role of mechanical forces in embryogenesis, ECM, and topology (surface) design to support human ESC self-renewal and pluripotency has been demonstrated [ 107 , 108 , 109 ]. It has been shown that the stiffness of the coating material modulates YAP activity in PSCs.…”

From mesenchymal niches to engineered in vitro model systems: Exploring and exploiting biomechanical regulation of vertebrate hedgehog signalling

“…The activation of ciliary signalling in mesenchyme during the development of tubular organs generates mechanical forces that also activate the Hippo pathway via Yes-associated protein (YAP, also called YAP1) and its related co-transcriptional factor TAZ, which promotes cell proliferation and inhibits apoptosis [ 211 ]. It has been shown that YAP restricts the Hh-dependent differentiation of smooth muscle [ 212 , 213 ]. This indicates the important role of primary cilia as mechanical responders and Hh signal transducers to regulate cellular adaptation to mechanical loadings.…”

The regulatory networks of the Hippo signaling pathway in cancer development

“…but also an essential regulator of cell response to these stimuli 46 .YAP/TAZ translates a series of signals from splicing pressure to cell morphology and extracellular matrix hardness and converts them into cell-specific transcriptional programs. This mechanism of transduction is essential to drive stem cell behavior and regeneration 47 .…”

“…In addition, when the cells growing on the soft substrate do not have enough area to stretch, the mesenchymal stem cells will differentiate into adipocytes. The cell morphology becomes round, and YAP/TAZ is mainly distributed in the cytoplasm; on the contrary, mesenchymal stem cells differentiate into osteoblasts, and the cell morphology is flat, YAP/TAZ mainly located in the nucleus 47 , 49 .…”