The molecular mechanism by which transcriptional factor DEC1 modulates circadian rhythms of blood pressure.

• Project/Area Number: 23390423
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Hiroshima University
• Principal Investigator: KATO Yukio 広島大学, 医歯薬保健学研究院, 研究員 (10112062)
• Co-Investigator(Kenkyū-buntansha): NOSHIRO Mitsuhide 広島大学, 医歯薬保健学研究院, 准教授 (00144858) ; KAWAMOTO Takeshi 広島大学, 医歯薬保健学研究院, 助教 (50224861) ; FUJIMOTO Katsumi 広島大学, 医歯薬保健学研究院, 助教 (40294566)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2013: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2011: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
• Keywords: 転写因子 / ノックアウトマウス / 血圧 / 時計遺伝子 / DEC1 / ﾉｯｸｱｳﾄﾏｳｽ / 2012/12/01

Research Abstract

Blood pressure shows a circadian variation, and many patients with cardiovascular diseases show disturbance in blood pressure circadian rhythm. We found that clock protein DEC1 binds and represses the E-boxes in the promoter of Atp1b1 gene, which encodes the beta subunit of Na/K-ATPase, whereas CLOCK activates these E-boxes. Consequently, the Atp1b1 mRNA and protein levels in the cardiovascular system showed circadian rhythms. Dec1-deficient mice showed decreased blood pressure, whereas clock-mutant mice showed increased blood pressure, as Na/K-ATPase is essential for the control of blood pressure. These findings revealed for the first time the molecular mechanism involved in blood pressure circadian rhythm.

Research Products

• [Journal Article] Seeding of mesenchymal stem cells into inner part of interconnected porous biodegradable scaffold by a new method with a filter paper (2014)
  • Author(s): Yamanaka K, Yamamoto K, Sakai Y, Suda Y, Shigemitsu Y, Kaneko T, Kato K, Kumagai T, Kato Y
  • Journal Title: Dental Materials Journal Volume: (in press)
  • NAID: 130004888175
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• [Journal Article] A novel protein, CHRONO, functions as a core component of the mammalian circadian clock. (2014)
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  • Journal Title: PLoS Biol. Volume: 12 Issue: 4 Pages: e1001839-e1001839
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  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Seeding of mesenchymal stem cells into inner part of interconnected porous biodegradable scaffold by a new method with a filter paper. (2014)
  • Author(s): Yamanaka K, Yamamoto K, Sakai Y, Suda Y, Shigemitsu Y, Kaneko T, Kato K, Kumagai T, Kato Y
  • Journal Title: Dental Materials Journal Volume: in press
  • NAID: 130004888175
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• [Journal Article] Different Circadian Expression of Major Matrix-Related Genes in Various Types of Cartilage : Modulation by Light-Dark Conditions (2013)
  • Author(s): Honda KK, Kawamoto T, Ueda HR, Nakashima A, Ueshima T, Yamada RG, Nishimura M, Oda R, Nakamura S, Kojima T, Noshiro M, Fujimoto K, Hashimoto S, Kato Y
  • Journal Title: J Biochem Volume: 154(4) Issue: 4 Pages: 373-81
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• [Journal Article] Age-dependent decrease in the chondrogenic potential of human bone marrow mesenchymal stem cells expanded with fibroblast growth factor-2 (2013)
  • Author(s): Kanawa M, Igarashi A, Ronald VS, Higashi Y, Kurihara H, Sugiyama M, Saskianti T, Pan H, Kato Y
  • Journal Title: Cytotherapy Volume: 15(9) Issue: 9 Pages: 1062-72
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• [Journal Article] Mesenchymal stem cells ameliorate experimental peritoneal fibrosis by suppressing inflammation and inhibiting TGF-beta1 signaling. (2013)
  • Author(s): Ueno, T., Nakashima, A., DOI:, S., Kawamoto, T., Honda, K., Yokoyama, Y., DOI:, T., Higashi, Y., Yorioka, N., Kato, Y., Kohno, N., and Masaki, T
  • Journal Title: Kidney Int Volume: 84(2) Issue: 2 Pages: 297-307
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• [Journal Article] Autologous Bone-Marrow Mesenchymal Stem Cell Implantation and Endothelial Function in a Rabbit Ischemic Limb Model (2013)
  • Author(s): Mikami S, Nakashima A, Nakagawa K, Maruhashi T, Iwamoto Y, Kajikawa M, Matsumoto T, Kihara Y, Chayama K, Noma K, Ochi M, Nishimura M, Tsuji K, Kato Y, Goto C, Higashi Y
  • Journal Title: PLOS ONE Volume: 8(7) Issue: 7 Pages: e67739-e67739
  • DOI: 10.1371/journal.pone.0067739
  • NAID: 120006986197
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• [Journal Article] ット変形性関節症モデルでの高分子ヒアルロン酸応答遺伝子の解析 (2013)
  • Author(s): 加藤幸夫, 本田清昌, 中島歩, 河本健
  • Journal Title: 臨床リウマチ Volume: 25(3) Pages: 174-184
• [Journal Article] ラット変形性関節症モデルでの高分子ヒアルロン酸応答遺伝子の解析 (2013)
  • Author(s): 加藤幸夫、本田清昌、中島歩、河本健
  • Journal Title: 臨床リウマチ Volume: 25 Pages: 174-184
  • Peer Reviewed
• [Journal Article] The basic helix-loop-helix transcription factor DEC2 inhibits TGF-beta-induced tumor progression in human pancreatic cancer BxPC-3 cells (2012)
  • Author(s): Sato, F., Kawamura, H., Kawamoto, T., Noshiro, M.,(他10名)
  • Journal Title: Int J Mol Med Volume: 30 Issue: 3 Pages: 495-501
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• [Journal Article] The BHLH transcription factor DEC1 plays an important role in the epithelial-mesenchymal transition of pancreatic cancer (2012)
  • Author(s): Wu, Y., Kawamoto, T., Noshiro, M., et al.(他10名)
  • Journal Title: Int J Oncol Volume: 41 Issue: 4 Pages: 1337-1346
  • DOI: 10.3892/ijo.2012.1559
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• [Journal Article] BHLH transcription factor DEC2 regulates pro-apoptotic factor Bim in human oral cancer HSC-3 cells (2012)
  • Author(s): Wu, Y., Sato, F., Bhawal, U.K., Kawamoto, T., Fujimoto, K., Noshiro, M., Seino, H., Morohashi, S., Kato, Y., Kijima, H
  • Journal Title: Biomedical Research Volume: 33 Issue: 2 Pages: 75-82
  • DOI: 10.2220/biomedres.33.75
  • NAID: 130004470811
  • ISSN: 0388-6107, 1880-313X
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• [Journal Article] Regulation of basic helix-loop-helix transcription factors Dec1 and Dec2 by RORα and their roles in adipogenesis. (2012)
  • Author(s): Ozaki N
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• [Journal Article] 循環器疾患における時計遺伝子DEC1の意義 (2012)
  • Author(s): 加藤幸夫他
  • Journal Title: Heart View Volume: 16 Pages: 103-107
• [Journal Article] Smad3 and Snail show circadian expression in human gingival fibroblasts, human mesenchymal stem cell, and in mouse liver Corresponding (2012)
  • Author(s): Sato F, et al
  • Journal Title: BBRC Volume: (In press)
  • Peer Reviewed
• [Journal Article] BHLH transcription factor DEC2 regulates pro-apoptotic factor Bim in human oral cancer HSC-3 cells (2012)
  • Author(s): Wu Y, et al
  • Journal Title: Biomedical Research Volume: (In press)
  • Peer Reviewed
• [Journal Article] Feasibility and limitations of the round robin test for assessment of in vitro chondrogenesis evaluation protocol in a tissue-engineered medical product (2011)
  • Author(s): Masako Yokoi, et al.
  • Journal Title: JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE Volume: (掲載確定)(印刷中)) Issue: 7 Pages: 550-558
  • DOI: 10.1002/term.460
  • Peer Reviewed
• [Journal Article] The effect of synthetic octacalcium phosphate in a collagen scaffold on the osteogenicity of mesenchymal stem cells (2011)
  • Author(s): Kawai T, Anada T, Masuda T, Honda Y, Sakai Y, Kato Y, Kamakura S, Echigo S, Suzuki O
  • Journal Title: European Cells and Materials Volume: 22 Pages: 124-136
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• [Journal Article] Impact of Zinc Fingers and Homeoboxes 3 (ZHX3) on the Regulation of Mesenchymal Stem Cell Osteogenic Differentiation (2011)
  • Author(s): Suehiro F, Nishimura M, Kawamoto T, Kanawa M, Yoshizawa Y, Murata H, Kato Y
  • Journal Title: Stem Cells Develop Volume: 20(9) Issue: 9 Pages: 1539-1547
  • DOI: 10.1089/scd.2010.0279
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• [Journal Article] PERIOD1 (PER1) has anti-apoptotic effects, and PER3 has pro-apoptotic effects during cisplatin (CDDP) treatment in human gingival cancer CA9-22 cells. (2011)
  • Author(s): Sato F, Wu Y, Bhawal UK, Liu Y, Imaizumi T, Morohashi S, Kato Y, Kijima H
  • Journal Title: Eur J Cancer Volume: 47(11) Issue: 11 Pages: 1747-58
  • DOI: 10.1016/j.ejca.2011.02.025
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• [Journal Article] Basic helix-loop-helix transcription factor DEC1 negatively regulates cyclin D1. Bhawal (2011)
  • Author(s): U.K., Sato, F., Arakawa, Y., Fujimoto, K., Kawamoto, T., Tanimoto, K., Ito, Y., Sasahira, T., Sakurai, T., Kobayashi, M., Kashima, I., Kijima, H., Kuniyasu, H., Abiko, Y., Kato, Y., Sato, S
  • Journal Title: J. Pathol Volume: 224(3) Issue: 3 Pages: 420-429
  • DOI: 10.1002/path.2878
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• [Journal Article] Basic helix-loop-helix transcription factors DEC1 and DEC2 regulate the paclitaxel-induced apoptotic pathway of MCF-7 human breast cancer cells (2011)
  • Author(s): Wu, Y., Sato, F., Kawamoto, T., Fujimoto, K., Noshiro, M., (他4名)
  • Journal Title: Int J Mol Med Volume: 27 Issue: 4 Pages: 491-495
  • DOI: 10.3892/ijmm.2011.617
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• [Journal Article] Mesenchymal stem cell-induced cranial suture-like gap in rats (2011)
  • Author(s): Kaku M, Tai M, Kawata T, Fujita T, Motokawa M, Ohtani J, Sakai Y, Kato Y, Tanne K
  • Journal Title: Plast Reconstr Surg Volume: 127(1) Issue: 1 Pages: 69-77
  • DOI: 10.1097/prs.0b013e3181f95849
  • Peer Reviewed
• [Journal Article] 無血清で増幅した間葉系幹細胞と歯髄細胞 (2011)
  • Author(s): 加藤幸夫, 藤井紗貴子, 五藤紀子, 北山和子, 金輪真佐美, 河本健, 藤本勝巳, 邵金昌, 桂由紀, 潘海鴎, 長谷川森一, 辻紘一郎
  • Journal Title: 広島歯科医学雑誌 Volume: 39(1) Pages: 1-8
• [Presentation] Isolation and expansion of mesenchymal stem cells from various tissues, including the umbilical cord, under serum-free conditions (2013)
  • Author(s): Yukio Kato, Jinchang Shao, Koichiro Tsuji
  • Organizer: Asia CORD
  • Place of Presentation: in Kobe, Japan
• [Presentation] 無血清で作製した他家ヒト滑膜MSC(TEC)への期待 (2013)
  • Author(s): 加藤幸夫
  • Organizer: 第12回日本再生医療学会
  • Place of Presentation: 横浜市
• [Presentation] Isolation and expansion of mesenchymal stem cells from various tissues, including the umbilical cord, under serum-free conditions (2013)
  • Author(s): Yukio Kato, Jinchang Shao, Koichro Tsuji
  • Organizer: Asia CORD2013
  • Place of Presentation: 神戸市
  • Invited
• [Presentation] 無血清で作製した他家ヒト滑膜MSC（TEC）への期待 (2013)
  • Author(s): 加藤幸夫
  • Organizer: 第12回 日本再生医療学会
  • Place of Presentation: 横浜市
  • Invited
• [Presentation] 培養環境全体の化学的規定化による移植用間葉系幹細胞の増殖, 分化の促進 (2012)
  • Author(s): 加藤幸夫
  • Organizer: (公)新化学技術推進協会ライフサイエンス技術部会・材料分科会
  • Place of Presentation: 東京都
  • Year and Date: 2012-09-18
• [Presentation] 膝関節症とヒアルロン酸への期待 (2012)
  • Author(s): 加藤幸夫, 辻紘一郎
  • Organizer: 第2回TOKYOヘルスコレクション
  • Place of Presentation: 東京都
  • Year and Date: 2012-03-15
• [Presentation] 再生医療用細胞(MSC など)の培養条件の完全化学規定化/至適化 (2012)
  • Author(s): 加藤幸夫
  • Organizer: 第11回再生医療の実用化に関するニーズ発表会
  • Place of Presentation: 神戸市
  • Year and Date: 2012-02-24
• [Presentation] 概日リズムを制御する新規時計エレメントEL-box の同定 (2012)
  • Author(s): 河本健, 能城光秀, 藤本勝巳, 加藤幸夫
  • Organizer: 第54回歯科基礎医学会学術大会・総会
  • Place of Presentation: 福島県郡山市
• [Presentation] Chemical Optimization of Both Culture Surfaces and Media Markedly Enhances MSC Proliferation (2012)
  • Author(s): Yukio Kato, Tania Saskianti, Masami Kanawa, Takeshi Kawamoto, Koichi Kato, Isao Hirata
  • Organizer: ISSCR Annual Meeting
  • Place of Presentation: Yokohama, Japan
• [Presentation] 各組織由来MSC の均質性と細胞表面マーカーの発現に及ぼす無血清培地(STK 培地)の影響 (2012)
  • Author(s): 長谷川森一, 邵金昌, 中村憲正, 松下隆, 金輪真佐美, 鈴木美紀, 原真依子, 辻紘一郎, 加藤幸夫
  • Organizer: 第11回日本再生医療学会
  • Place of Presentation: 横浜市
• [Presentation] 無血清培地(STK 系列培地)を用いた間葉系幹細胞からのTissue Engineered Construct(TEC)作成 (2012)
  • Author(s): 邵金昌, 長谷川森一, 杉田憲彦, 森口悠, 下村和範, 原真依子, 桂由紀, 坂井将典, 河原裕美, 弓削類, 加藤幸夫, 辻紘一郎, 吉川秀樹, 中村憲正
  • Organizer: 第11回日本再生医療学会
  • Place of Presentation: 横浜市
• [Presentation] Enhanced Proliferation of Stem Cells from Deciduous Teeth in Serum-free Media (2012)
  • Author(s): Noriko Goto, Katsumi Fujimoto, Shin-ichi Hasegawa, Kazuko Kitayama, Veronica Sainik Ronald, Katsuyuki Kozai, Yukio Kato
  • Organizer: STK1/STK2 8th Biennial Conference PDAA(Pediatric Dentistry Association of Asia)
  • Place of Presentation: Bali , Indonesia
• [Presentation] Enhanced Proliferation of Stem Cells from Deciduous Teeth in Serum-free Media, STK1/STK2 (2012)
  • Author(s): Noriko Goto,et al.
  • Organizer: 8th Biennial Conference PDAA(Pediatric Dentistry Association of Asia)
  • Place of Presentation: Bali , Indonesia
• [Presentation] 無血清培地（STK系列培地）を用いた間葉系幹細胞からのTissue Engineered Construct(TEC)作成 (2012)
  • Author(s): 邵金昌他
  • Organizer: 第11回 日本再生医療学会
  • Place of Presentation: 横浜市
• [Presentation] 各組織由来MSCの均質性と細胞表面マーカーの発現に及ぼす無血清培地（STK培地）の影響 (2012)
  • Author(s): 長谷川森一他
  • Organizer: 第11回 日本再生医療学会
  • Place of Presentation: 横浜市
• [Presentation] 無血清培地で培養したヒト滑膜由来MSCの未分化性・軟骨分化能の検討 (2012)
  • Author(s): 中田恭輔他
  • Organizer: 第11回 日本再生医療学会
  • Place of Presentation: 横浜市
• [Presentation] 概日リズムを制御する新規時計エレメントEL-boxの同定 (2012)
  • Author(s): 河本健他
  • Organizer: 第54回歯科基礎医学会学術大会・総会
  • Place of Presentation: 福島県郡山市
• [Presentation] Chemical Optimization of Both Culture Surfaces and Media Markedly Enhances MSC Proliferation (2012)
  • Author(s): Yukio Kato,et al.
  • Organizer: ISSCR Annual Meeting
  • Place of Presentation: Yokohama
  • Invited
• [Presentation] 培養環境全体の化学的規定化による移植用間葉系幹細胞の増殖、分化の促進 (2012)
  • Author(s): 加藤幸夫
  • Organizer: （公）新化学技術推進協会ライフサイエンス技術部会・材料分科会
  • Place of Presentation: 東京都
  • Invited
• [Presentation] 体内時計の異常は高血圧など生活習慣病を誘発する : 分子レベルでの解析 (2011)
  • Author(s): 加藤幸夫
  • Organizer: 第17回岐阜糖尿病・内分泌疾患研究会
  • Place of Presentation: 岐阜市
  • Year and Date: 2011-02-10
• [Presentation] Serum-Free Cultures for Human Mesenchymal Stem Cells using Defined Culture Surfaces (2011)
  • Author(s): Yukio Kato
  • Organizer: 1st Meeting of Surabaya Regenerative Medicine and Stem Cell Centre (SRMSC), 2nd Meeting of Indonesia Association of Tissue Bank (IATB), SYMPOSIUM
  • Place of Presentation: Surabaya, Indonesia
• [Presentation] 核内受容体ROR α による時計遺伝子DEC1, DEC2 の発現調節と脂肪分化 (2011)
  • Author(s): 尾崎徳継, 能城光秀, 河本健, 福崎麗, 藤本勝巳, 丹根一夫, 加藤幸夫
  • Organizer: 第52回日本生化学会中国・四国支部例会
  • Place of Presentation: 広島市
• [Presentation] 間葉系幹細胞の増殖・分化ならびにインテクリン発現に対する転写因子GATA6 の作用 (2011)
  • Author(s): 道田将彦, 河本健, 能城光秀, 藤本勝巳, 金輪真佐美, 尾崎徳継, 笹本智子, 丹根一夫, 加藤幸夫
  • Organizer: 第52回日本生化学会中国・四国支部例会
  • Place of Presentation: 広島市
• [Presentation] 間葉系幹細胞の軟骨分化におけるDEC2 の役割 (2011)
  • Author(s): 笹本智子, 藤本勝巳, 金輪真佐美, 河本健, 能城光秀, 道田将彦, 尾崎徳継, 丹根一夫, 加藤幸夫
  • Organizer: 第52回日本生化学会中国・四国支部例会
  • Place of Presentation: 広島市
• [Presentation] 細胞表面抗原を指標とした口腔内からの骨前駆細胞の分取 (2011)
  • Author(s): 鎌田浩一, 藤本勝巳, 西村正宏, 末廣史雄, 貞森紳丞, 赤川安正, 加藤幸夫
  • Organizer: 第52回日本生化学会中国・四国支部例会
  • Place of Presentation: 広島市
• [Presentation] Identification of HMGA2 and SIM2 interaction in MSC (2011)
  • Author(s): Tania Saskianti, Takeshi Kawamoto , Yukio Kato
  • Organizer: 3rd International Workshop on BioDental Education & Research Hiroshima University Graduate School of Biomedical Sciences
  • Place of Presentation: 広島市
• [Presentation] Effect of conditioned medium derived from mouse ameloblast lineage cells on differentiation of human dental pulp cells (2011)
  • Author(s): Sakiko Fujii, Katsumi Fujimoto, Fusanori Nishimura, Yukio Kato
  • Organizer: 3rd International Workshop on BioDental Education & Research Hiroshima University Graduate School of Biomedical Sciences
  • Place of Presentation: 広島市
• [Presentation] Expression profiles of nuclear receptors and their functions in rat growth plate Chondrocytes (2011)
  • Author(s): Noritsugu Ozaki, Mitsuhide Noshiro, Kiyomasa Honda, Takeshi Kawamoto, Katsumi Fujimoto, Kazuo Tanne, Yukio Kato
  • Organizer: 3rd International Workshop on BioDental Education & Research Hiroshima University Graduate School of Biomedical Sciences
  • Place of Presentation: 広島市
• [Presentation] Transcription factors regulating differentiation of MSC (2011)
  • Author(s): Takeshi Kawamoto, Hiroshi Kubo, Tomoyuki Iwata, Katsumi Fujimoto, Mitsuhide Noshiro, Yukio Kato
  • Organizer: 3rd International Workshop on BioDental Education & Research Hiroshima University Graduate School of Biomedical Sciences
  • Place of Presentation: 広島市
• [Presentation] Serum-Free Cultures for Human Mesenchymal Stem Cells using Defined Culture Surfaces (2011)
  • Author(s): Yukio Kato
  • Organizer: 1^<st> Meeting of Surabaya Regenerative Medicine and Stem Cell Centre (SRMSC), 2^<nd> Meeting of Indonesia Association of Tissue Bank (IATB), SYMPOSIUM
  • Place of Presentation: Surabaya, Indonesia(招待講演)
• [Presentation] 間葉系幹細胞の軟骨分化におけるDEC2の役割 (2011)
  • Author(s): 笹本智子, 他
  • Organizer: 第52回日本生化学会中国・四国支部例会
  • Place of Presentation: 広島市
• [Presentation] 間葉系幹細胞の増殖・分化ならびにインテクリン発現に対する転写因子GATA6の作用 (2011)
  • Author(s): 道田将彦, 他
  • Organizer: 第52回日本生化学会中国・四国支部例会
  • Place of Presentation: 広島市
• [Presentation] 核内受容体RORαによる時計遺伝子DEC1,DEC2の発現調節と脂肪分化 (2011)
  • Author(s): 尾崎徳継, 他
  • Organizer: 第52回日本生化学会中国・四国支部例会
  • Place of Presentation: 広島市
• [Book] DEC1/STRA13/SHARP2 and DEC2/SHARP1 coordinate physiological processes, including circadian rhythms in response to environmental stimuli. bHLH Factors in Development and Disease : Current topics in developmental biology (2014)
  • Author(s): Kato Y, Kawamoto T, Fujimoto K, Noshiro M
  • Publisher: Elsevier(in press)
• [Book] bHLH Factors in Development and Disease: Current topics in developmental biology (2014)
  • Author(s): Kato Y, Kawamoto T, Fujimoto K, Noshiro M.
  • Publisher: Elsevier
• [Book] 幹細胞用無血清培地の開発, 幹細胞医療の実用化技術と産業展望 第3章幹細胞の維持培養と分化誘導 (2013)
  • Author(s): 加藤幸夫, 邵金昌, 長谷川森一, 西村正宏, 桂由紀, 中村憲正, 辻紘一郎
  • Total Pages: 293
  • Publisher: (株)シーエムシー出版刊
• [Book] 幹細胞医療の実用化技術と産業展望 (2013)
  • Author(s): 加藤幸夫、邵金昌、長谷川森一、西村正宏、桂由紀、中村憲正、辻紘一郎他
  • Total Pages: 293
  • Publisher: （株）シーエムシー出版
• [Book] 幹細胞医療の実用化技術と産業展望 (2013)
  • Author(s): 加藤幸夫他
  • Total Pages: 293
  • Publisher: （株）シーエムシー出版
• [Patent(Industrial Property Rights)] 動物細胞培養キット、動物細胞の培養方法及び動物細胞の選択培養方法 (2011)
  • Inventor(s): 加藤幸夫、平田伊佐雄、金輪真佐美
  • Industrial Property Rights Holder: 広島大学
  • Industrial Property Number: 2011-084119
  • Filing Date: 2011-04-05