Cellular conversion from non- skeletal to skeletal cells by using transactivation MyoD domain

• Project/Area Number: 25670784
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Morphological basic dentistry
• Research Institution: Tsurumi University
• Principal Investigator: NIFUJI Akira 鶴見大学, 歯学部, 教授 (00240747)
• Co-Investigator(Kenkyū-buntansha): ARAKI Ryoko 国立研究開発法人放射線医学総合研究所, 研究基盤センター, 室長 (40392211) ; NAKASHIMA Kazuhisa 鶴見大学, 歯学部, 講師 (90252692) ; IDENO Hisashi 鶴見大学, 歯学部, 学部助手 (40435699)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 遺伝子 / 分化 / 転写因子 / 骨格系組織 / 遺伝子発現 / 分化転換 / 転写活性 / MyoD

Outline of Final Research Achievements

Sets of specific transcription factors may induce cellular conversion from one committed cell to another. In the mesenchylmal cell lineages, the transcription factor MyoD can induce non-muscle cells to muscle cells. It is also reported that co-transfection of Sox9 with other sets of transcription factors may induce chondrocytes from non- chondrocytes. However reproducible and highly efficient cellular conversion from non- skeletal to skeletal cells is still challenging. In this study, we examined whether cellular conversion from non- skeletal to skeletal cells can be improved by using transactivation domain (TAD) of MyoD. Addition of TAD to Runx2 and sox9 enhanced activity of transcriptional transactivation. Cellular conversion rates by those factors did not change significantly, suggesting that additional factors or improvement of experimental condition are required for the cellular conversion of non- skeletal cells.

Research Products

• [Journal Article] Coordinated expression of H3K9 histone methyltransferases during tooth development in mice. (2015)
  • Author(s): Kamiunten T, Ideno H, Shimada A, Nakamura Y, Kimura H, Nakashima K, Nifuji A.
  • Journal Title: Histochemistry and Cell Biology. Volume: 143 Pages: 259-266
  • DOI: 10.1007/s00418-014-1284-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Efficient expansion of mouse primary tenocytes using a novel collagen gel culture method. (2014)
  • Author(s): Akemi Shimada, Satoshi Wada, Kouji Inoue, Hisashi Ideno, Taichi Kamiunten, Koichiro Komatsu, Akira Kudo, Yoshiki Nakamura,et al
  • Journal Title: Histochemistry and Cell Biology. Volume: (in press) Pages: 205-215
  • DOI: 10.1007/s00418-014-1191-4
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Search for Conditions to Detect Epigenetic Marks and Nuclear Proteins in Immunostaining of the Testis and Cartilage (2014)
  • Author(s): Hisashi Ideno, Akemi Shimada, Taichi Kamiunten, Kazuhiko Imaizumi, Yoshiki Nakamura,et al
  • Journal Title: Journal of Histology Volume: (in press)
  • DOI: 10.1155/2014/658293
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Promotion of Bone Formation around Alendronate-immobilized Screw-Type Titanium Implants after Implantation into Rat Molar Tooth Sockets (2014)
  • Author(s): Raita, Y, Komatsu, K, Nifuji, A, Sato, M, Morito, M, Hayakawa, T
  • Journal Title: J. Hard Tissue Biology. Volume: 23 Issue: 2 Pages: 177-186
  • DOI: 10.2485/jhtb.23.177
  • NAID: 130004480650
  • Peer Reviewed / Open Access
• [Journal Article] Predominant expression of H3K9 methyltransferases in prehypertrophic and hypertrophic chondrocytes during mouse growth plate cartilage development. (2013)
  • Author(s): Ideno H, Shimada A, Imaizumi K, Kimura H, Abe M, Nakashima K, and Nifuji A
  • Journal Title: Gene Expr Patterns. Volume: 13 Pages: 84-90
  • DOI: 10.1016/j.gep.2013.01.002
  • Peer Reviewed
• [Journal Article] Alendronate promotes bone formation by inhibiting protein prenylation in osteoblasts in rat tooth replantation model. (2013)
  • Author(s): Komatsu K, Shimada A, Shibata T, Wada S, Ideno H, Nakashima K, Amizuka N, Noda M, Nifuji A.
  • Journal Title: J Endocrinology Volume: 219 Pages: 145-158
  • DOI: 10.1530/joe-13-0040
  • Peer Reviewed
• [Journal Article] Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells. (2013)
  • Author(s): Ryoko Araki
  • Journal Title: Nature. Volume: 494 Pages: 100-104
  • DOI: 10.1038/nature11807
  • Peer Reviewed
• [Journal Article] Molecular mechanisms of skeletal tissue formation (2013)
  • Author(s): Nifuji A
  • Journal Title: JPFSM Volume: 2 Issue: 1 Pages: 1-8
  • DOI: 10.7600/jpfsm.2.1
  • NAID: 10031159011
  • Peer Reviewed
• [Presentation] Expressions and functions of Histone H3K9 methyltransferases during tooth development (2014)
  • Author(s): Taichi Kamiunten , Hisahi Ideno, Akemi Shimada, Satoshi Wada, Yoshiki Nakamura, Makoto Tachibana, Kazuhisa Nakashima, Akira Nifuji
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（ 神奈川県）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] Annexin A5 null mice show masticatory muscle hypertrophy, hyper tooth attrition and bony outgrowth in the orofacial region (2014)
  • Author(s): Akemi Shimada 1, Yoshinori Arai 2, Koichiro Komatsu 1, Kazuhisa Nakashima 1, Teruhito Yamashita 3, Naoyuki Takahashi 3, Ernst Pöschl 4, Akira Nifuji 1
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（ 神奈川県）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] Functions of histone methyltransferase G9a during growth and differentiation of mesenchymal cells (2014)
  • Author(s): Ideno H1,4, Shimada A1, Kamiunten T2, Wada S2, Komatsu K1, Tachibana M3, Araki R4, Nakamura Y2, Abe M4, Nakashima K1, Nifuji A1,4
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（ 神奈川県）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] The functions of histone methyltransferase G9a during growth and differentiation of mesenchymal cells (2014)
  • Author(s): 出野 尚1,4, 島田明美1, 上運天太一2, 和田悟史2, 小松浩一郎1, 立花 誠3, 荒木良子4, 中村芳樹2, 安倍真澄4, 中島和久1,二藤 彰1,4
  • Organizer: 第56回 歯科基礎医学会
  • Place of Presentation: 福岡国際会議場（ 福岡県）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Functions of the histone methyltransferase G9a during tenocyte differentiation (2014)
  • Author(s): 和田悟史、出野 尚、島田明美、上運天太一、中島和久、中村芳樹、二藤 彰
  • Organizer: 第56回 歯科基礎医学会
  • Place of Presentation: 福岡国際会議場（ 福岡県）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 歯の発生分化におけるヒストンメチル化酵素の発現と機能 (2014)
  • Author(s): 上運天太一、出野尚、島田明美、中島和久、中村芳樹、二藤 彰
  • Organizer: 第56回 歯科基礎医学会
  • Place of Presentation: 福岡国際会議場（ 福岡県）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] ヒストン3リジン9メチル化酵素群（G9a、Glp、Suv39h1、Prdm2）のマウ ス歯牙発生における発現と機能 (2014)
  • Author(s): 上運天太一、島田明美、出野尚、中村芳樹、中島和久、二藤彰
  • Organizer: 第32回 日本骨代謝学会
  • Place of Presentation: 大阪国際会議場（ 大阪府）
  • Year and Date: 2014-07-24 – 2014-07-26
• [Presentation] 間葉系細胞の増殖・分化過程におけるヒストンメチル化酵素G9aの機能 (2014)
  • Author(s): 出野 尚1,2, 島田明美1, 上運天太一3, 和田悟史3, 小松浩一郎1, 中島和久1, 荒木良子2, 安倍真澄2, 二藤 彰1,2
  • Organizer: 第32回 日本骨代謝学会
  • Place of Presentation: 大阪国際会議場（ 大阪府）
  • Year and Date: 2014-07-24 – 2014-07-26
• [Presentation] ヒストンメチル化酵素G9aによる腱細胞の分化制御 (2014)
  • Author(s): 和田悟史、島田明美、出野尚、中村芳樹、中島和久、二藤 彰
  • Organizer: 第32回 日本骨代謝学会
  • Place of Presentation: 大阪国際会議場（ 大阪府）
  • Year and Date: 2014-07-24 – 2014-07-26
• [Presentation] 効率的で安定的なマウス腱細胞の初代培養法 (2014)
  • Author(s): 島田明美1, 和田悟史2, 出野尚1, 上運天太一2, 小松浩一郎1, 工藤明3, 中村芳樹2, 中島和久1, 二藤 彰1
  • Organizer: 第32回 日本骨代謝学会
  • Place of Presentation: 大阪国際会議場（ 大阪府）
  • Year and Date: 2014-07-24 – 2014-07-26
• [Presentation] Predominant expression of Histone 3 lysine 9 methyltransferases in the prehypertrophc chondrocytes during the growth plate chondrocyte development (2013)
  • Author(s): Ideno H, Shimada A, Kamiunten T, Imaizumi, K, Nakashima K, Nifuji A
  • Organizer: 2nd Joint Meeting of the International Bone and Mineral Society and The Japanese Society for Bone and Mineral Research
  • Place of Presentation: 神戸国際会議場 兵庫県
• [Presentation] Three histone 3 lysine 9 methyltransferases , G9a, GLP, and SETDB1, are expresssed during mouse tooth development. (2013)
  • Author(s): Kamiunten T, Shimada A, Ideno H, , Nakashima K, Nakamura Y, Nifuji A
  • Organizer: 2nd Joint Meeting of the International Bone and Mineral Society and The Japanese Society for Bone and Mineral Research
  • Place of Presentation: 神戸国際会議場 兵庫県
• [Presentation] Tenocytes regulate cell survical of osteoblasts in vitro. (2013)
  • Author(s): Wada S, Shimada A, Ideno H, Nakamura Y, Nakashima K, Nifuji A
  • Organizer: 2nd Joint Meeting of the International Bone and Mineral Society and The Japanese Society for Bone and Mineral Research
  • Place of Presentation: 神戸国際会議場 兵庫県
• [Presentation] Endocytic incorporation of alendronate promotes bone formation (2013)
  • Author(s): Komatsu K, Shimada A, Ideno H, Shibata T, Nakashima K, Amizuka N, Noda M, Nifuji A
  • Organizer: 2nd Joint Meeting of the International Bone and Mineral Society and The Japanese Society for Bone and Mineral Research
  • Place of Presentation: 神戸国際会議場 兵庫県
• [Presentation] 発生の骨格組織分化におけるH3K9メチル化酵素群の発現局在 (2013)
  • Author(s): 二藤彰、 島田明美、 中島和久
  • Organizer: 第55回歯科基礎医学会学術大会
  • Place of Presentation: 岡山コンベンションセンター 岡山県
• [Presentation] MyoD mediated myogenic conversion from fibroblasts into myoblasts is blocked by cell cycle inhibition (2013)
  • Author(s): Hisashi Ideno, Kazuhisa Nakashima, Yasuyuki Ohkawa, Hiroshi Kimura , Ryoko Araki , Masumi Abe , Akira Nifuji
  • Organizer: 第３６回 日本分子生物学会
  • Place of Presentation: 神戸国際会議場 兵庫県
• [Presentation] Histone 3 lysine 9 methyltransferases , G9a, GLP, SUV39h1, and PRDM2, are expresssed during mouse tooth development. (2013)
  • Author(s): Kamiunten T, Ideno H, Shimada A, Nakamura Y, Nakashima K, Kimura H, Nifuji A
  • Organizer: 第３６回 日本分子生物学会
  • Place of Presentation: 神戸国際会議場 兵庫県
• [Presentation] Regulations of osteoblastic survival at entheses. (2013)
  • Author(s): Wada S, Shimada A, Ideno H, Nakamura Y, Nakashima K, Nifuji A
  • Organizer: 第３６回 日本分子生物学会
  • Place of Presentation: 神戸国際会議場 兵庫県