{"@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/1390001205036740352.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.11406/rinketsu.58.942"}},{"identifier":{"@type":"PMID","@value":"28883279"}},{"identifier":{"@type":"NDL_BIB_ID","@value":"028514178"}},{"identifier":{"@type":"URI","@value":"http://id.ndl.go.jp/bib/028514178"}},{"identifier":{"@type":"URI","@value":"https://ndlsearch.ndl.go.jp/books/R000000004-I028514178"}},{"identifier":{"@type":"NAID","@value":"130006067976"}},{"identifier":{"@type":"URI","@value":"https://search.jamas.or.jp/link/ui/2017376959"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@language":"ja","@value":"造血幹細胞の老化制御に対するテロメア結合因子Pot1aの機能解析"},{"@language":"en","@value":"Functional analysis of Protection of Telomeres 1a (Pot1a) in regulation of hematopoietic stem cell aging"},{"@language":"ja-Kana","@value":"ゾウケツ カンサイボウ ノ ロウカ セイギョ ニ タイスル テロメア ケツゴウ インシ Pot1a ノ キノウ カイセキ"}],"dc:language":"ja","description":[{"type":"abstract","notation":[{"@language":"en","@value":"<p>Repeated cell divisions induce DNA damage accumulation, which impairs stem cell function during aging. However, the general molecular mechanisms by which this occurs remain unclear. Herein, we show that the expression of protection of telomeres 1a (Pot1a), a component of shelterin, is crucial for prevention of telomeric DNA damage response (DDR) and maintenance of hematopoietic stem cell (HSC) activity during aging. We observed that HSCs express high levels of Pot1a during development, and this expression declines with aging. Knockdown of Pot1a induced an age-related phenotype, characterized by increased telomeric DDR and reduced long-term reconstitution activity. In contrast, treatment with exogenous Pot1a protein prevented telomeric DDR, which decreased stem cell activity and partially rejuvenated HSC activity. These results highlight a general, reversible mechanism by which aging compromises mammalian stem cell activity, with widespread implications for regenerative medicine.</p>"},{"@language":"ja","@value":"<p>繰り返し起こる細胞分裂や老化に伴ってDNA損傷が蓄積し幹細胞機能が低下するが，その分子機構には不明な点が多い。今回我々はshelterin複合体の構成因子の一つ，Pot1aの造血幹細胞における発現は，テロメアDNAの損傷応答の抑制や，老化に伴って低下する幹細胞活性を維持するのに重要であることを明らかにした。まず我々は，Pot1aは造血幹細胞において高発現し，老化と共に低下することを見出した。またPot1aを発現抑制すると，テロメアDNAの損傷応答が増加し，造血幹細胞が老化の表現型を呈し，長期骨髄再構成能も著しく低下することが分かった。一方で，外因性Pot1aタンパク質処理を行うことによって，テロメアDNAの損傷応答を抑制し，造血幹細胞活性の低下を抑えることができた。また，老化した造血幹細胞においても幹細胞活性を一部回復させる効果があった。今回の知見は，老化による幹細胞の活性低下を抑制する技術の開発，および医療応用の基盤となることが期待される。</p>"}],"abstractLicenseFlag":"disallow"}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1420564276179795072","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"90569584"},{"@type":"NRID","@value":"1000090569584"},{"@type":"NRID","@value":"9000016704985"},{"@type":"NRID","@value":"9000365620809"},{"@type":"NRID","@value":"9000251861553"}],"foaf:name":[{"@language":"ja","@value":"細川 健太郎"},{"@language":"en","@value":"HOSOKAWA Kentaro"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University"},{"@language":"ja","@value":"九州大学大学院　医学研究院　応用幹細胞医科学部門　幹細胞再生修復医学分野"}]},{"@id":"https://cir.nii.ac.jp/crid/1410001205036740352","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000365620810"}],"foaf:name":[{"@language":"ja","@value":"Ben D MACARTHUR"},{"@language":"en","@value":"MACARTHUR Ben D"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Centre for Human Development, Stem Cells and Regeneration, Institute for Developmental Sciences, University of Southampton"},{"@language":"ja","@value":"英国サウサンプトン大学　発達科学研究所"}]},{"@id":"https://cir.nii.ac.jp/crid/1420845751146419712","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"00571366"},{"@type":"NRID","@value":"1000000571366"},{"@type":"NRID","@value":"9000365620811"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/181101"}],"foaf:name":[{"@language":"ja","@value":"生島 芳子"},{"@language":"en","@value":"IKUSHIMA Yoshiko"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Molecular Diabetic Medicine, National Center for Global Health and Medicine"},{"@language":"ja","@value":"国立国際医療研究センター研究所　糖尿病研究センター　分子糖尿病医学研究部"}]},{"@id":"https://cir.nii.ac.jp/crid/1410001205036740359","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000365620812"}],"foaf:name":[{"@language":"ja","@value":"外山 弘文"},{"@language":"en","@value":"TOYAMA Hirofumi"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, School of Medicine, Keio University"},{"@language":"ja","@value":"慶應義塾大学医学部　坂口記念講座　発生・分化生物学"}]},{"@id":"https://cir.nii.ac.jp/crid/1420001326204942848","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"00336083"},{"@type":"NRID","@value":"1000000336083"},{"@type":"NRID","@value":"9000004728614"},{"@type":"NRID","@value":"9000004410978"},{"@type":"NRID","@value":"9000238936702"},{"@type":"NRID","@value":"9000365620813"},{"@type":"NRID","@value":"9000004730597"},{"@type":"NRID","@value":"9000004730430"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0212535"}],"foaf:name":[{"@language":"ja","@value":"舛廣 善和"},{"@language":"en","@value":"MASUHIRO Yoshikazu"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Laboratory of Molecular and Cellular Physiology, Department of Applied Biological Sciences, College of Bioresource Sciences, Nihon University"},{"@language":"ja","@value":"日本大学　生物資源科学部　応用生物科学科"}]},{"@id":"https://cir.nii.ac.jp/crid/1030003658711159809","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"60060258"},{"@type":"NRID","@value":"1000060060258"},{"@type":"NRID","@value":"9000365620814"},{"@type":"NRID","@value":"9000004731826"},{"@type":"NRID","@value":"9000253011841"},{"@type":"NRID","@value":"9000019140395"},{"@type":"NRID","@value":"9000254852071"},{"@type":"NRID","@value":"9000254347712"},{"@type":"NRID","@value":"9000254850614"},{"@type":"NRID","@value":"9000021060981"},{"@type":"NRID","@value":"9000403892549"},{"@type":"NRID","@value":"9000022093776"},{"@type":"NRID","@value":"9000022085527"},{"@type":"NRID","@value":"9000392757764"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0023546"}],"foaf:name":[{"@language":"ja","@value":"花澤 重正"},{"@language":"en","@value":"HANAZAWA Shigemasa"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Laboratory of Molecular and Cellular Physiology, Department of Applied Biological Sciences, College of Bioresource Sciences, Nihon 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年生"},{"@language":"en","@value":"SUDA Toshio"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Cancer Science Institute of Singapore, National University of Singapore"},{"@language":"ja","@value":"シンガポール国立大学　シンガポールがん科学研究所"}]},{"@id":"https://cir.nii.ac.jp/crid/1420001326237103104","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"90365403"},{"@type":"NRID","@value":"1000090365403"},{"@type":"ORCID","@value":"0000-0003-1936-4907"},{"@type":"NRID","@value":"9000253395891"},{"@type":"NRID","@value":"9000244898107"},{"@type":"NRID","@value":"9000345422468"},{"@type":"NRID","@value":"9000001683036"},{"@type":"NRID","@value":"9000282418738"},{"@type":"NRID","@value":"9000251861185"},{"@type":"NRID","@value":"9000340442957"},{"@type":"NRID","@value":"9000018839793"},{"@type":"NRID","@value":"9000001336339"},{"@type":"NRID","@value":"9000000504636"},{"@type":"NRID","@value":"9000403586815"},{"@type":"NRID","@value":"9000001730398"},{"@type":"NRID","@value":"9000412568203"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0121479"}],"foaf:name":[{"@language":"ja","@value":"新井 文用"},{"@language":"en","@value":"ARAI Fumio"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University"},{"@language":"ja","@value":"九州大学大学院　医学研究院　応用幹細胞医科学部門　幹細胞再生修復医学分野"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"04851439"},{"@type":"LISSN","@value":"04851439"},{"@type":"EISSN","@value":"18820824"},{"@type":"NDL_BIB_ID","@value":"000000024253"},{"@type":"ISSN","@value":"04851439"},{"@type":"NCID","@value":"AN00252940"}],"prism:publicationName":[{"@language":"en","@value":"Rinsho Ketsueki"},{"@language":"ja","@value":"臨床血液"},{"@language":"en","@value":"Rinsho Ketsueki"},{"@language":"en","@value":"Jpn. J. Clin. Hematol."},{"@language":"en","@value":"The Japanese Journal of Clinical Hematology"},{"@language":"ja","@value":"臨床血液"}],"dc:publisher":[{"@language":"en","@value":"The Japanese Society of Hematology"},{"@language":"ja","@value":"一般社団法人 日本血液学会"}],"prism:publicationDate":"2017","prism:volume":"58","prism:number":"8","prism:startingPage":"942","prism:endingPage":"949"},"reviewed":"true","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","url":[{"@id":"http://id.ndl.go.jp/bib/028514178"},{"@id":"https://ndlsearch.ndl.go.jp/books/R000000004-I028514178"},{"@id":"https://search.jamas.or.jp/link/ui/2017376959"}],"availableAt":"2017","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Hematopoietic%20stem%20cell","dc:title":"Hematopoietic stem cell"},{"@id":"https://cir.nii.ac.jp/all?q=DNA%20damage","dc:title":"DNA damage"},{"@id":"https://cir.nii.ac.jp/all?q=Aging","dc:title":"Aging"},{"@id":"https://cir.nii.ac.jp/all?q=Pot1","dc:title":"Pot1"},{"@id":"https://cir.nii.ac.jp/all?q=Hematopoietic%20stem%20cell","dc:title":"Hematopoietic stem cell"},{"@id":"https://cir.nii.ac.jp/all?q=DNA%20damage","dc:title":"DNA damage"},{"@id":"https://cir.nii.ac.jp/all?q=Aging","dc:title":"Aging"},{"@id":"https://cir.nii.ac.jp/all?q=Pot1","dc:title":"Pot1"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040000782280752384","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"26221309"},{"@type":"JGN","@value":"JP26221309"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-26221309/"}],"notation":[{"@language":"ja","@value":"造血幹細胞のホメオスターシスの維持と破綻"},{"@language":"en","@value":"Homeostasis of hematopoietic stem cells and its breakdown"}]},{"@id":"https://cir.nii.ac.jp/crid/1040282256945457664","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"17K09907"},{"@type":"JGN","@value":"JP17K09907"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17K09907/"}],"notation":[{"@language":"ja","@value":"造血幹細胞の未分化性維持に対する転写因子Foxp2の機能解析"},{"@language":"en","@value":"Function of Foxp2 in the maintenance of hematopoietic stem cells."}]}],"dataSourceIdentifier":[{"@type":"JALC","@value":"oai:japanlinkcenter.org:2003194585"},{"@type":"NDL_SEARCH","@value":"oai:ndlsearch.ndl.go.jp:R000000004-I028514178"},{"@type":"PUBMED","@value":"28883279"},{"@type":"CIA","@value":"130006067976"},{"@type":"KAKEN","@value":"PRODUCT-21660631"},{"@type":"KAKEN","@value":"PRODUCT-21491374"},{"@type":"OPENAIRE","@value":"pmid_dedup__::86e19884befa14067035836bbd52e6f6"}]}