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大学・研究所にある論文を検索できる 「PAX9は歯根膜細胞の細胞外マトリックスを制御することにより、iPS細胞の歯根膜幹細胞様細胞への分化に関与する」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

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PAX9は歯根膜細胞の細胞外マトリックスを制御することにより、iPS細胞の歯根膜幹細胞様細胞への分化に関与する

杉浦, 梨紗 SUGIURA, Risa スギウラ, リサ 九州大学

2023.03.20

概要

九州大学学術情報リポジトリ
Kyushu University Institutional Repository

PAX9 Is Involved in Periodontal Ligament Stem
Cell-like Differentiation of Human-Induced
Pluripotent Stem Cells by Regulating
Extracellular Matrix
杉浦, 梨紗

https://hdl.handle.net/2324/6787537
出版情報:Kyushu University, 2022, 博士(歯学), 課程博士
バージョン:
権利関係:© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open
access article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license.

(様式3)







杉浦

梨紗

論 文 名 :PAX9 Is Involved in Periodontal Ligament Stem Cell-like Differentiation of HumanInduced Pluripotent Stem Cells by Regulating Extracellular Matrix
(PAX9 は歯根膜細胞の細胞外マトリックスを制御することにより、iPS 細胞の歯
根膜幹細胞様細胞への分化に関与する)





:甲



文 内









歯根膜幹細胞は、歯根膜組織の恒常性維持、修復、再生において中心的な役割を担っており、現在臨
床へ応用できる十分な数の歯根膜幹細胞を安全かつ効率的に獲得する方法の樹立が求められている。
我々はこれまでに、iPS 細胞由来の神経堤細胞様細胞(iNC 細胞)を、特定のヒト歯根膜細胞由来の細
胞外マトリックス(ECM)上で培養し、歯根膜幹細胞様細胞(iPDLSC)を誘導する方法を確立した
(Hamano et al. 2018)。しかしながら、iNC 細胞から iPDLSC への分化を制御する主な因子について
は不明である。そこで本研究では、iPDLSC への分化において重要なヒト歯根膜細胞由来の ECM の産
生を制御する転写因子を同定することとした。2 種類のヒト歯根膜細胞(HPDLC-3S、HPDLC-3U)お
よびヒト皮膚線維芽細胞(HDF)の ECM 上で iNC 細胞を培養した。HPDLC-3U 由来の ECM 上で培
養した iNC 細胞は、HDF および HPDLC-3S 由来の ECM 上で培養した iNC 細胞と比較し、有意に高
い歯根膜幹細胞様細胞関連遺伝子の発現と多分化能を示した。そこで、CAGE 法を用いて HPDLC-3U,
HPDLC-3S および HDF における転写因子の網羅的解析を行い、HPDLC-3U において発現が高い転写
因子 5 つを抽出した。HPDLC-3U, HPDLC-3S および HDF において、この 5 つの転写因子の発現を
確認した結果、HPDLC-3S および HDF と比較して HPDLC-3U では転写因子 PAX9 の発現が有意に
高かった。次に、転写因子 PAX9 の siRNA を導入した HPDLC-3U の ECM 上にて iNC 細胞を培養し、
得られた細胞の歯根膜幹細胞様細胞関連遺伝子の発現、増殖能、表面抗原および多分化能について解析
を行った。siPAX9 を導入した HPDLC-3U の ECM 上にて培養した iNC 細胞は、コントロールと比較
して歯根膜幹細胞様細胞関連遺伝子の発現ならびに脂肪細胞様細胞への分化能が低下した。一方、増殖
能、表面抗原および骨芽細胞様細胞への分化能は変わらなかった。このことから、PAX9 はヒト歯根膜
細胞の ECM 産生を制御する転写因子の 1 つであり、iNC 細胞の iPDLSC への分化に関与しているこ
とが示唆された。

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