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j.scr.2021.102287.pdf | 5.68 MB | Adobe PDF | 見る/開く |
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dc.contributor.author | Yuzuriha, Akinori | en |
dc.contributor.author | Nakamura, Sou | en |
dc.contributor.author | Sugimoto, Naoshi | en |
dc.contributor.author | Kihara, Shunsuke | en |
dc.contributor.author | Nakagawa, Masato | en |
dc.contributor.author | Yamamoto, Takuya | en |
dc.contributor.author | Sekiguchi, Kiyotoshi | en |
dc.contributor.author | Eto, Koji | en |
dc.contributor.alternative | 杠, 明憲 | ja |
dc.contributor.alternative | 中村, 壮 | ja |
dc.contributor.alternative | 杉本, 直志 | ja |
dc.contributor.alternative | 中川, 誠人 | ja |
dc.contributor.alternative | 山本, 拓也 | ja |
dc.contributor.alternative | 江藤, 浩之 | ja |
dc.date.accessioned | 2021-04-07T05:51:20Z | - |
dc.date.available | 2021-04-07T05:51:20Z | - |
dc.date.issued | 2021-05 | - |
dc.identifier.uri | http://hdl.handle.net/2433/262473 | - |
dc.description | 血液細胞へ効率よく変化させる弱い接着を明らかに --血液細胞の産生効率を向上--. 京都大学プレスリリース. 2021-03-31. | ja |
dc.description | Stuck stem cells are no good at making blood. 京都大学プレスリリース. 2021-03-31. | en |
dc.description.abstract | Recombinant matrices have enabled feeder cell-free maintenance cultures of human pluripotent stem cells (hPSCs), with laminin 511-E8 fragment (LM511-E8) being widely used. However, we herein report that hPSCs maintained on LM511-E8 resist differentiating to multipotent hematopoietic progenitor cells (HPCs), unlike hPSCs maintained on LM421-E8 or LM121-E8. The latter two LM-E8s bound weakly to hPSCs compared with LM511-E8 and activated the canonical Wnt/β-catenin signaling pathway. Moreover, the extracellular LM-E8-dependent preferential hematopoiesis was associated with a higher expression of integrin β1 (ITGB1) and downstream integrin-linked protein kinase (ILK), β-catenin and phosphorylated JUN. Accordingly, the lower coating concentration of LM511-E8 or addition of a Wnt/β-catenin signaling activator, CHIR99021, facilitated higher HPC yield. In contrast, the inhibition of ILK, Wnt or JNK by inhibitors or mRNA knockdown suppressed the HPC yield. These findings suggest that extracellular laminin scaffolds modulate the hematopoietic differentiation potential of hPSCs by activating the ITGB1-ILK-β-catenin-JUN axis at the undifferentiated stage. Finally, the combination of low-concentrated LM511-E8 and a revised hPSC-sac method, which adds bFGF, SB431542 and heparin to the conventional method, enabled a higher yield of HPCs and higher rate for definitive hematopoiesis, suggesting a useful protocol for obtaining differentiated hematopoietic cells from hPSCs in general. | en |
dc.language.iso | eng | - |
dc.publisher | Elsevier BV | en |
dc.rights | © 2021 The Authors. Published by Elsevier B.V. This is an open access article under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Public License (CC BY-NC-ND license) | en |
dc.subject | Hematopoietic cell differentiation | en |
dc.subject | Laminin | en |
dc.subject | Integrin β1 | en |
dc.subject | ILK | en |
dc.subject | Canonical Wnt/β-catenin pathway | en |
dc.subject | Pluripotent stem cells | en |
dc.title | Extracellular laminin regulates hematopoietic potential of pluripotent stem cells through integrin β1-ILK-β-catenin-JUN axis | en |
dc.type | journal article | - |
dc.type.niitype | Journal Article | - |
dc.identifier.jtitle | Stem Cell Research | en |
dc.identifier.volume | 53 | - |
dc.relation.doi | 10.1016/j.scr.2021.102287 | - |
dc.textversion | publisher | - |
dc.identifier.artnum | 102287 | - |
dc.address | Department of Clinical Application, CiRA, Kyoto University | en |
dc.address | Department of Clinical Application, CiRA, Kyoto University | en |
dc.address | Department of Clinical Application, CiRA, Kyoto University | en |
dc.address | Department of Fundamental Cell Technology, CiRA, Kyoto University | en |
dc.address | Department of Life Science Frontiers, CiRA, Kyoto University | en |
dc.address | Department of Life Science Frontiers, CiRA, Kyoto University; Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University; AMED-CREST | en |
dc.address | Division of Matrixome Research and Application, Institute for Protein Research, Osaka University | en |
dc.address | Department of Clinical Application, CiRA, Kyoto University; Department of Regenerative Medicine, Chiba University Graduate School of Medicine | en |
dc.identifier.pmid | 33813173 | - |
dc.relation.url | https://www.cira.kyoto-u.ac.jp/j/pressrelease/news/210331-160000.html | - |
dc.relation.url | https://www.cira.kyoto-u.ac.jp/e/pressrelease/news/210323-170000.html | - |
dcterms.accessRights | open access | - |
datacite.awardNumber | 18J14237 | - |
datacite.awardNumber | 18H04164 | - |
datacite.awardNumber.uri | https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18J14237/ | - |
datacite.awardNumber.uri | https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-18H04164/ | - |
dc.identifier.pissn | 1873-5061 | - |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.awardTitle | 多能性幹細胞を用いた赤血球輸血製剤の大量安定供給システムの構築 | ja |
jpcoar.awardTitle | 乱流依存性血小板産生機構の分子基盤の解明と生体外製造システムへの応用 | ja |
jpcoar.funderName.alternative | Japan Society for the Promotion of Science (JSPS) | en |
jpcoar.funderName.alternative | Japan Society for the Promotion of Science (JSPS) | en |
出現コレクション: | 学術雑誌掲載論文等 |
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