Establishment of iPS cells from McCune-Albright syndrome and it application

• Project/Area Number: 16K15791
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Tokyo Dental College
• Principal Investigator: Yamaguchi Akira 東京歯科大学, 歯学部, 客員教授 (00142430)
• Co-Investigator(Kenkyū-buntansha): 小野寺 晶子 東京歯科大学, 歯学部, 講師 (90637662) ; 齋藤 暁子 東京歯科大学, 歯学部, 助教 (90722835)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: McCune-Albright 症候群 / iPS細胞 / GNAS / McCune-Albright症候群 / 線維性骨異形成症 / GNAS1 / 歯学 / 病理学

Outline of Final Research Achievements

Since distribution of the gene mutated cells in McCune-Albright syndrome (MAS) occurs depending somatic mosaicism, we applied gene editing technique using CRISPR/Cas9 system to generate human iPS cells exhibiting GNAS1 mutation observed in MAS. We obtained 2 clones exhibiting GAS1 mutation among 24 clones. These iPS cells showed undifferentiated markers and those identifying three germ layers. Thus we successfully established human iPS cells retaining GNAS1 mutaion observed in MAS.

Research Products

• [Journal Article] Leukemia inhibitory factor produced by fibroblasts within tumor stroma participates in invasion of oral squamous cell carcinoma. (2018)
  • Author(s): Ohata Y, Tsuchiya M, Hirai H, Yamaguchi S, Akashi T, Sakamoto K, Yamaguchi A, Ikeda T, Kayamori K
  • Journal Title: PLos One Volume: 13 Issue: 2 Pages: e0191865-e0191865
  • DOI: 10.1371/journal.pone.0191865
  • Peer Reviewed / Open Access
• [Journal Article] Targeted reversion of induced pluripotent stem cells from patients with human cleidocranial dysplasia showed corrected osteoblastic differentiation both in vitro and in vivo. (2018)
  • Author(s): Ooki A, Nakamura T, Onodera S, Hayashi K, Hasegawa D, Kato H, Onda T, Watanabe A, Kosaki K, Nishimura K, Ohtaka M, Nakanishi M, Sakamoto T, Yamaguchi A, Sueishi K, Azuma T
  • Journal Title: Stem Cell Res Ther Volume: 9 Issue: 1 Pages: 12-12
  • DOI: 10.1186/s13287-017-0754-4
  • Peer Reviewed / Open Access
• [Journal Article] The HIV co-receptor CCR5 regulates osteoclast function. (2017)
  • Author(s): Lee JW, Hoshino A, Inoue K, Saitou T, Uehara S, Kobayashi Y, Ueha S, Matsushima K, Yamaguchi A, Imai Y, Iimura T.
  • Journal Title: Nat Commun Volume: 8 Issue: 1 Pages: 2226-2226
  • DOI: 10.1038/s41467-017-02368-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Gorlin syndrome-derived induced pluripotent stem cells are hypersensitive to Hedgehog-mediated osteogenic induction. (2017)
  • Author(s): Hasegawa D, Shino H, Onodera S, Nakamura T, Saito A, Onda T, Watanabe K, Nishimura K, Ohtaka M, Nakanishi M, Kosaki K, Yamaguchi A, Shibahara T, Azuma T
  • Journal Title: PLos One Volume: 12 Issue: 10 Pages: e0186879-e0186879
  • DOI: 10.1371/journal.pone.0186879
  • Peer Reviewed / Open Access
• [Journal Article] Multi-layered mutatin in hedgehog-related genes in Gorlin syndrome may affect the phenotype. (2017)
  • Author(s): Onodera S, Saito A, Hasegawa D, Watanabe K, Morita N, Nomura T, Shibahara T, Ohba S, Yamaguchi A, Azuma T
  • Journal Title: PLOS ONE Volume: 12 Issue: 9 Pages: e0184702-e0184702
  • DOI: 10.1371/journal.pone.0184702
  • Peer Reviewed / Open Access
• [Journal Article] Genetic basis of calcifying cystic odontogenic tumors. (2017)
  • Author(s): Yukimori A, Oikawa Y, Morita K, Nguyen CTK, Harada H, Yamaguchi, S, Kayamori K, Yamaguchi A, Ikeda T, Sakamoto K
  • Journal Title: PLos One Volume: 12 Issue: 6 Pages: e0180224-e0180224
  • DOI: 10.1371/journal.pone.0180224
  • Peer Reviewed / Open Access
• [Journal Article] Practical whole-tooth restoration utilizing autologous bioengineered tooth germ transplantation in a postnatal canine model. (2017)
  • Author(s): Ono M, Oshima M, Ogawa M, Sonoyama W, Hara ES, Oida Y, Shinkawa S, Nakajima R , Mine A ,Hayano S, Fukumoto S , Kasugai8 S , Yamaguchi A, Tsuji T, Kuboki T
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 44522-44522
  • DOI: 10.1038/srep44522
  • NAID: 120006535050
  • Peer Reviewed / Open Access
• [Journal Article] The Bone Regeneration Model and Primary Osteoblastic Cell Culture Used in the Analysis of Ccn3 Transgenic and Knockout Mice (2017)
  • Author(s): Sakamoto K, Matsushita Y, Minamizato T, Katsuki Y, Katsube KI, Yamaguchi A
  • Journal Title: Methods Mol Biol Volume: 1489 Pages: 309-324
  • Peer Reviewed
• [Journal Article] LAMC2 is a predictive marker for malignant progression of leukoplakia. (2017)
  • Author(s): Nguyen CTK, Okamura T, Morita K, Miki Y, Izumo T, Kayamori K, Yamaguchi A, Sakamoto K
  • Journal Title: J Oral Pathol Med Volume: 46 Issue: 3 Pages: 223-231
  • DOI: 10.1111/jop.12485
  • Peer Reviewed
• [Journal Article] Parathyroid hormone facilitates osteogenesis differently in cancellous and cortical bones. (2016)
  • Author(s): Ogura K, Iimura T, Makino Y, Sugie-Oya A, Shimomura A, Takao-Kawabata R, Ishizuya T, Moriyama K, Yamaguchi A
  • Journal Title: Bone Reports Volume: 5 Pages: 7-14
  • DOI: 10.1016/j.bonr.2016.01.002
  • Peer Reviewed / Open Access
• [Journal Article] NOTCH3 Is Induced in Cancer-Associated Fibroblasts and Promotes Angiogenesis in Oral Squamous Cell Carcinoma (2016)
  • Author(s): Kayamori K, Katsube K, Sakamoto K, Ohyama Y, Hirai H, Yukimori A, Ohata Y, Akashi T, Saitoh M, Harada K, Harada H, Yamaguchi A
  • Journal Title: PLoS ONE Volume: 11 Issue: 4 Pages: 223-231
  • DOI: 10.1371/journal.pone.0154112
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] KRT17 is induced in oral cancer and facilitate tumor gowth. (2016)
  • Author(s): Khanom R, Nguyen CTK, Kayamori K, Zhao X, Morita K, Yamaguchi A, Sakamoto K
  • Journal Title: PlosOne Volume: 11 Issue: 8 Pages: e0161163-e0161163
  • DOI: 10.1371/journal.pone.0161163
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] THBS1 is induced by TGFB1 in the cancer stroma and promotes invasion of oral squamous cell carcinoma. (2016)
  • Author(s): Pal SK, Nguyen CTK, Morita, K, Miki Y, Kayamori K, Yamaguchi A, Sakamoto K
  • Journal Title: J Oral Pathol Med Volume: 45 Issue: 10 Pages: 730-739
  • DOI: 10.1111/jop.12430
  • Peer Reviewed / Open Access
• [Journal Article] A ficile one-step strategy for the egeneration of conditional knockout mice to explore the role of Notch1 in oroesophageal tumrigenesis (2016)
  • Author(s): Mandasari M, Sawangarun W, Ktsube K, Kayamori K, Yamaguchi A, Sakamoto K
  • Journal Title: Biochem Bioph Res Co Volume: 469 Pages: 61-767
  • Peer Reviewed / Open Access
• [Presentation] THの骨形成促進作用における基礎研究の展開 (2017)
  • Author(s): 山口 朗
  • Organizer: 第7回骨・軟骨フロンティア
  • Invited
• [Presentation] iPS 細胞を用いた顎骨疾患病態解明へのアプローチ (2017)
  • Author(s): 東 俊文、小野寺晶、齋藤 暁子、中村 貴、大庭 伸介、小崎健次郎、 山口 朗、柴原 孝彦
  • Organizer: 第５９回歯科基礎医学会総会学術大会アップデートシンポジウム
  • Invited
• [Presentation] ステオネットワークの構築・維持・破綻：顎顔面骨疾患の病態解析の基盤構築（宿題報告） (2016)
  • Author(s): 山口 朗
  • Organizer: 第70回NPO法人日本口腔科学会学術集会
  • Place of Presentation: 広島市
  • Invited
• [Presentation] 歯学研究における基礎と臨床のシグナル伝達 (2016)
  • Author(s): 山口 朗
  • Organizer: 第５８回歯科基礎医学会学術大会日本学術会議シンポジウム
  • Place of Presentation: 札幌市
  • Invited
• [Book] 最新口腔外科学 (2017)
  • Author(s): 山口 朗、栢森高
  • Publisher: 医歯薬出版株式会社