Role of Simulated Microgravity on Mechanically-induced Nuclear Shuttling of of YAP/TAZ in Mesenchymal Stem Cells
Additional Funding Sources
This study was supported in-part by an Idaho NASA EPSCoR Research Initiation grant under Award No. IIA-1301792 and a NASA Idaho Space Consortium Seed grant. We also acknowledge support from The Biomolecular Research Center at Boise State with funding from an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under Grants No. P20GM103408 and P20GM109095, the National Science Foundation, Grant Nos. 0619793 and 0923535, the MJ Murdock Charitable Trust, and the Idaho State Board of Education.
Abstract
Bone deterioration in spaceflight is in part driven by reduced functionality of mesenchymal stem cells (MSC) that replace and regenerate musculoskeletal tissues by sensing and responding to environmental cues. In MSCs, mechanotransducers YAP and TAZ play critical roles in regulating growth and differentiation. The functionality of YAP/TAZ signaling requires them to shuttle into the nucleus to activate their target genes. Recent work from our group shows that altered gravity conditions in simulated microgravity (sMG) significantly decreased cell proliferation and compromised nuclear structure. This suggests that loss of form in sMG can compromise YAP/TAZ signaling in MSCs. Therefore, our main motivation is to identify the microgravity-mediated alterations in YAP/TAZ levels, compartmentalization and nuclear shuttling in response to mechanical stimuli. Here we hypothesize that sMG will decrease YAP/TAZ shuttling into nucleus in response to low intensity vibration (LIV, 90Hz, 0.7g) and mechanical strain (0.2Hz, 2%). YAP/TAZ compartmentalization will be compared between sMG treated MSCs and non-sMG controls after either acute single session of LIV or strain using cell fractionation and western blot analysis. Findings from this study will be critical for understanding the effects of spaceflight on MSC growth and differentiation via YAP/TAZ signaling.
Role of Simulated Microgravity on Mechanically-induced Nuclear Shuttling of of YAP/TAZ in Mesenchymal Stem Cells
Bone deterioration in spaceflight is in part driven by reduced functionality of mesenchymal stem cells (MSC) that replace and regenerate musculoskeletal tissues by sensing and responding to environmental cues. In MSCs, mechanotransducers YAP and TAZ play critical roles in regulating growth and differentiation. The functionality of YAP/TAZ signaling requires them to shuttle into the nucleus to activate their target genes. Recent work from our group shows that altered gravity conditions in simulated microgravity (sMG) significantly decreased cell proliferation and compromised nuclear structure. This suggests that loss of form in sMG can compromise YAP/TAZ signaling in MSCs. Therefore, our main motivation is to identify the microgravity-mediated alterations in YAP/TAZ levels, compartmentalization and nuclear shuttling in response to mechanical stimuli. Here we hypothesize that sMG will decrease YAP/TAZ shuttling into nucleus in response to low intensity vibration (LIV, 90Hz, 0.7g) and mechanical strain (0.2Hz, 2%). YAP/TAZ compartmentalization will be compared between sMG treated MSCs and non-sMG controls after either acute single session of LIV or strain using cell fractionation and western blot analysis. Findings from this study will be critical for understanding the effects of spaceflight on MSC growth and differentiation via YAP/TAZ signaling.
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