Fluid shear stress promotes embryonic stem cell pluripotency via interplay between β‐catenin and vinculin in bioreactor culture

In this study, we investigated how murine embryonic stem cells (mESCs) sense fluid shear stress and modulate a noncanonical Wnt signaling response to promote pluripotency. mESCs showed higher expression of pluripotency marker genes, Oct4, Sox2, and Nanog in the absence of leukemia inh ibitory factor (LIF) in stirred suspension bioreactors compared to adherent culture, a phenomenon we have termed mechanopluripotency. In bioreactor culture, fluid shear promoted the nuclear translocation of the less well‐known pluripotency regulator β‐catenin and concomitant increase of c‐Myc expression, an upstream regulator of Oct4, Sox2, and Nanog. We also observed similar β‐catenin nuclear translocation in LIF‐free mESCs cultured on E‐cadherin substrate under defined fluid shear stress conditions in flow chamber plates. mESCs showed lower shear‐induced expression of pluripo tency marker genes when β‐catenin was inhibited, suggesting that β‐catenin signaling is crucial to mESC mechanopluripotency. Key to this process is vinculin, which is known to rearrange and associate more strongly with adherens junctions in response to fluid shear. When the vinculin gene is di srupted, we observe that nuclear β‐catenin translocation and mechanopluripotency are abrogated. Our results indicate that mechanotransduction through the adherens junction complex is important for mESC pluripotency maintenance.
Source: Stem Cells - Category: Stem Cells Authors: Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research