{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1390577618925172992.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.2142/biophysico.bppb-v20.0018"}},{"identifier":{"@type":"URI","@value":"https://www.jstage.jst.go.jp/article/biophysico/20/2/20_e200018/_pdf"}},{"identifier":{"@type":"URI","@value":"https://search.jamas.or.jp/link/ui/2024256075"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@language":"en","@value":"Guideline for design of substrate stiffness for mesenchymal stem cell culture based on heterogeneity of YAP and RUNX2 responses"}],"dc:language":"en","description":[{"type":"abstract","notation":[{"@language":"en","@value":"<p>Mesenchymal stem cells (MSCs) have the potential for self-renewal and multipotency to differentiate into various lineages. Thus, they are of great interest in regenerative medicine as a cell source for tissue engineering. Substrate stiffness is one of the most extensively studied exogenous physical factors; however, consistent results have not always been reported for controlling MSCs. Conventionally used stiff culture substrates, such as tissue-culture polystyrene and glass, enhance nuclear localization of a mechanotransducer YAP and a pre-osteogenic transcription factor RUNX2, and bias MSCs towards the osteogenic lineage, even without osteogenic-inducing soluble factors. The mechanosensitive nature and intrinsic heterogeneity present challenges for obtaining reproducible results. This review summarizes the heterogeneity in human MSC response, specifically, nuclear/cytoplasmic localization changes in the mechanotransducer yes-associated protein (YAP) and the osteogenic transcription factor RUNX2, in response to substrate stiffness. In addition, a perspective on the intracellular factors attributed to response heterogeneity is discussed. The optimal range of stiffness parameters, Young’s modulus, for MSC expansion culture to suppress osteogenic differentiation bias through the suppression of YAP and RUNX2 nuclear localization, and cell cycle progression is likely to be surprisingly narrow for a cell population from an identical donor and vary among cell populations from different donors. We believe that characterization of the heterogeneity of MSCs and understanding their biological meaning is an exciting research direction to establish guidelines for the design of culture substrates for the sophisticated control of MSC properties.</p>"}],"abstractLicenseFlag":"disallow"}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1410577618925172993","@type":"Researcher","personIdentifier":[{"@type":"ORCID","@value":"0000-0003-2314-2119"}],"foaf:name":[{"@language":"en","@value":"Miyoshi Hiromi"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Mechanical Systems Engineering, Graduate School of Systems Design, Tokyo Metropolitan University"}]},{"@id":"https://cir.nii.ac.jp/crid/1410577618925172992","@type":"Researcher","foaf:name":[{"@language":"en","@value":"Yamazaki Masashi"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Mechanical Systems Engineering, Graduate School of Systems Design, Tokyo Metropolitan University"}]},{"@id":"https://cir.nii.ac.jp/crid/1410577618925172995","@type":"Researcher","foaf:name":[{"@language":"en","@value":"Fujie Hiromichi"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Mechanical Systems Engineering, Graduate School of Systems Design, Tokyo Metropolitan University"}]},{"@id":"https://cir.nii.ac.jp/crid/1420282801193785984","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"10336018"},{"@type":"NRID","@value":"1000010336018"},{"@type":"NRID","@value":"9000018555914"},{"@type":"NRID","@value":"9000412281495"},{"@type":"NRID","@value":"9000402585467"},{"@type":"NRID","@value":"9000006869316"},{"@type":"NRID","@value":"9000021468926"},{"@type":"NRID","@value":"9000003794580"},{"@type":"NRID","@value":"9000017713506"},{"@type":"NRID","@value":"9000023392726"},{"@type":"NRID","@value":"9000406357922"},{"@type":"NRID","@value":"9000255959990"},{"@type":"NRID","@value":"9000410177519"},{"@type":"NRID","@value":"9000331417138"},{"@type":"NRID","@value":"9000329413038"},{"@type":"NRID","@value":"9000308712667"},{"@type":"NRID","@value":"9000406375519"},{"@type":"NRID","@value":"9000017714157"},{"@type":"NRID","@value":"9000017712206"},{"@type":"NRID","@value":"9000329413324"},{"@type":"NRID","@value":"9000244012260"},{"@type":"NRID","@value":"9000000013447"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/satorukid_0101"}],"foaf:name":[{"@language":"en","@value":"Kidoaki Satoru"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Institute for Materials Chemistry and Engineering, Kyushu University"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"21894779"},{"@type":"LISSN","@value":"21894779"}],"prism:publicationName":[{"@language":"en","@value":"Biophysics and Physicobiology"},{"@language":"ja","@value":"Biophysics and Physicobiology"},{"@language":"en","@value":"BIOPHYSICS"}],"dc:publisher":[{"@language":"en","@value":"The Biophysical Society of Japan"},{"@language":"ja","@value":"一般社団法人 日本生物物理学会"}],"prism:publicationDate":"2023","prism:volume":"20","prism:number":"2","prism:startingPage":"n/a"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","url":[{"@id":"https://www.jstage.jst.go.jp/article/biophysico/20/2/20_e200018/_pdf"},{"@id":"https://search.jamas.or.jp/link/ui/2024256075"}],"availableAt":"2023","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=osteogenic%20differentiation","dc:title":"osteogenic differentiation"},{"@id":"https://cir.nii.ac.jp/all?q=regenerative%20medicine","dc:title":"regenerative medicine"},{"@id":"https://cir.nii.ac.jp/all?q=mechanotransducer","dc:title":"mechanotransducer"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040848250603394816","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"19H05627"},{"@type":"JGN","@value":"JP19H05627"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19H05627/"}],"notation":[{"@language":"ja","@value":"局在プラズモンシートによる細胞接着ナノ界面の超解像度ライブセルイメージング"},{"@language":"en","@value":"Super-resolution live-cell imaging of cell-attached nanointerface using LSPR sheets"}]},{"@id":"https://cir.nii.ac.jp/crid/1040851707391076352","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"21K18326"},{"@type":"JGN","@value":"JP21K18326"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21K18326/"}],"notation":[{"@language":"ja","@value":"細胞メカノ活性化効果を最適化する非一様力学場培養技術の開発"},{"@language":"en","@value":"Development of a culture technique using heterogeneous mechanical fields optimized for cellular mechano-activation"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360002219091574272","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Hippo pathway regulation by cell morphology and stress fibers"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011145776957952","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Overexpression of Cbfa1 in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011145874893952","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011146250982272","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Role of YAP/TAZ in 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