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However, the hydrodynamic environment in the bioreactor can modulate PSC behavior, pluripotency and differentiation potential in ways that need to be well\u2009understood. 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 inhibitory 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 \u03b2-catenin and concomitant increase of c-Myc expression, an upstream regulator of Oct4, Sox2, and Nanog. We also observed similar \u03b2-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 pluripotency marker genes when \u03b2-catenin was inhibited, suggesting that \u03b2-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 disrupted, we observe that nuclear \u03b2-catenin translocation and mechanopluripotency are abrogated. Our results indicate that mechanotransduction through the adherens junction complex is important for mESC pluripotency maintenance.<\/jats:p>","DOI":"10.1002\/stem.3382","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T09:59:49Z","timestamp":1636624789000},"page":"1166-1177","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Fluid Shear Stress Promotes Embryonic Stem Cell Pluripotency via Interplay Between \u03b2-Catenin and Vinculin in Bioreactor Culture"],"prefix":"10.1093","volume":"39","author":[{"given":"Suman C.","family":"Nath","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Cumming School of Medicine University of Calgary, Calgary, Alberta, Canada"},{"name":"McCaig Institute for Bone and Joint Health, Cumming School of Medicine University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley","family":"Day","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Cumming School of Medicine University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lane","family":"Harper","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Cumming School of Medicine University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Yee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Cumming School of Medicine University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlie Yu-Ming","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Cumming 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Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Kallos","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone and Joint Health, Cumming School of Medicine University of Calgary, Calgary, Alberta, Canada"},{"name":"Pharmaceutical Production Research Facility, Schulich School of Engineering University of Calgary, Calgary, Alberta, Canada"},{"name":"Department of Chemical and Petroleum Engineering, Schulich School of Engineering University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derrick E.","family":"Rancourt","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Cumming School of Medicine University of Calgary, Calgary, Alberta, Canada"},{"name":"McCaig Institute for Bone and Joint Health, Cumming School of Medicine University of Calgary, Calgary, Alberta, Canada"},{"name":"Department of Medical Genetics, Cumming 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