Elucidation of liver carcinogenesis mechanism by epigenetic reprogramming.

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659593
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: General surgery
• Research Institution: Yokohama City University
• Principal Investigator: SEKINE Keisuke 横浜市立大学, 医学部, 助教 (00323569)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 癌 / エピジェネティクス

Research Abstract

As a result of introduction of the 4 factors to the HCC cell lines, colonies of iPS cell-like is formed after about 2 weeks. The established clones were investigated by morphological observation, gene expression analysis and the transplantation into immunodeficient mice. Expression of hepatocyte marker HNF4 in comparison with HCC cell lines were decreased. And increased expression of Sox2, undifferentiated marker, was observed. However, the expression of undifferentiated markers were lower compared with iPS cells. To verify the presence or absence of teratoma formation capability, clones were transplanted into the testes of immunodeficient mice (NOD / scid). However no teratoma formation was observed from clones that were established in this study.

Research Products

• [Journal Article] Tropism of cancer stem cells to a specific distant organ (2014)
  • Author(s): Okuda R, Sekine K, Hisamatsu D, Ueno Y, Takebe T, Zheng YW, Taniguchi H
  • Journal Title: In Vivo Volume: 28(3) Pages: 361-5
  • Peer Reviewed
• [Journal Article] The CD133+CD44+ Precancerous Subpopulation of Oval Cells is a Therapeutic Target for Hepatocellular (2014)
  • Author(s): Zheng YW, Tsuchida T, Shimao T, Li B, Takebe T, Zhang RR, Sakurai Y, Ueno Y, Sekine K, Ishibashi N, Imajima M, Tanaka T, Taniguchi H
  • Journal Title: Carcinoma Stem Cells Dev Volume: (in press)
  • Peer Reviewed
• [Journal Article] Fluorescent labeling and visualization of human induced pluripotent stem cells with the use of transcription activatore like effector nucleases (2014)
  • Author(s): Sekine K, Takebe T, Taniguchi H
  • Journal Title: Transplant Proc Volume: 46(4) Pages: 1205-7
  • DOI: 10.1016/j.transproceed.2014.02.003
  • Peer Reviewed
• [Journal Article] Ring1B promotes hepatic stem/ progenitor cell expansion via simultaneous suppression of Cdkn1a and Cdkn2a (2014)
  • Author(s): Koike H, Ueno Y, Naito T, Shiina T, Nakata S, Ouchi R, Obana Y, Sekine K, Zheng YW,Takebe T, Isono KI, Koseki H, Taniguchi H
  • Journal Title: Hepatology
  • DOI: 10.1002/hep.27046
  • Peer Reviewed
• [Journal Article] Engineering of human hepatic tissue with functional vascular networks (2014)
  • Author(s): Takebe T, Koike N, Sekine K, Fujiwara R, Amiya T, Zheng YW, Taniguchi H
  • Journal Title: Organogenesis Volume: 10(2)(Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Generation of a vascularized and functional human liver from an iPSC-derived organ bud transplant (2014)
  • Author(s): Takebe T, Zhang RR, Koike H, Kimura M, Yoshizawa E, Enomura M, Koike N, Sekine K, Taniguchi H
  • Journal Title: Nature Protocols Volume: 9 Pages: 396-409
  • DOI: 10.1038/nprot.2014.020
  • Peer Reviewed
• [Journal Article] Evidence of a sophisticatedly heterogeneous population of human umbilical vein endothelial cells (2014)
  • Author(s): Zheng YW, Nie YZ, Tsuchida T, Zhang RR, Aoki K, Sekine K, Ogawa M, Takebe T, Ueno Y, Sakakibara H, Hirahara F, Taniguchi H
  • Journal Title: Transplant Proc Volume: 46(4) Pages: 1251-3
  • DOI: 10.1016/j.transproceed.2013.11.077
  • Peer Reviewed
• [Journal Article] Identification of proliferating human hepatic cells from human induced pluripotent stem cells (2014)
  • Author(s): Zhang R, Takebe T, Sekine K, Koike H, Zheng Y, Taniguchi H
  • Journal Title: Transplant Proc Volume: 46(4) Pages: 1201-4
  • DOI: 10.1016/j.transproceed.2013.12.021
  • Peer Reviewed
• [Journal Article] The development of humanized liver with Rag1 knockout rats (2014)
  • Author(s): Tsuchida T, Zheng YW, Zhang RR, Takebe T, Ueno Y, Sekine K, Taniguchi H
  • Journal Title: Transplant Proc Volume: 46(4) Pages: 1191-3
  • DOI: 10.1016/j.transproceed.2013.12.026
  • Peer Reviewed
• [Journal Article] High-resolution intravital imaging for monitoring the transplanted islets in mice (2014)
  • Author(s): Takahashi Y, Takebe T, Enomura M, Koike N, Lee S, Nemeno JG, Sekine K, Lee JI, Taniguchi H
  • Journal Title: Transplant Proc Volume: 46(4) Pages: 1166-8
  • DOI: 10.1016/j.transproceed.2013.11.089
  • Peer Reviewed
• [Journal Article] Vascularized and functional human liver tissue from an induced pluripotent stem cell-derived organ bud transplant (2013)
  • Author(s): Takebe T, Sekine K, Enomura M, Koike H, Kimura M, Ogaeri T, Zhang RR, Ueno Y, Zheng YW, Koike N, Aoyama S, Adachi Y, Taniguchi H
  • Journal Title: Nature Volume: 499(7459) Pages: 481-484
  • DOI: 10.1038/nature12271
  • Peer Reviewed
• [Journal Article] The generation of pancreaticβ-cell spheroids in a simulated microgravity culture system (2013)
  • Author(s): Tanaka H, Tanaka S, Sekine K, Kita S, Okamura A, Takebe T, Zheng YW, Ueno Y, Tanaka J and Taniguchi H
  • Journal Title: Biomaterials Volume: 34(23) Pages: 5785-5791
  • DOI: 10.1016/j.biomaterials.2013.04.003
  • Peer Reviewed
• [Journal Article] Vitamin D Receptor in osteoblasts Is a negative regulator of bone mass control (2013)
  • Author(s): Yamamoto Y, Yoshizawa T, Fukuda T, Shirode-Fukuda Y, Yu T, Sekine K, Sato T, Kawano H, Aihara KI, Nakamichi Y, Watanabe T, Shindo M, Inoue K, Inoue E, Tsuji N, Hoshino M, Karsenty G, Metzger D, Chambon P, Kato S, Imai Y
  • Journal Title: Endocrinology Volume: 154(3) Pages: 1008-1020
  • DOI: 10.1210/en.2012-1542
  • Peer Reviewed
• [Journal Article] Establishment of Automated Culture System for Induced Pluripotent Stem Cells (2012)
  • Author(s): Koike H, Kubota K, Sekine K, Takebe T, Zheng YW, Ueno Y, Tanigawa N, Taniguchi H
  • Journal Title: BMC Biotechnol Volume: 12 Pages: 81
  • DOI: 10.1186/1472-6750-12-81
  • Peer Reviewed
• [Journal Article] Inhibition of Stabilin-2 elevates the circulating hyaluronic acid level and prevents tumor metastasis (2012)
  • Author(s): Hirose Y, Saijou E, Sugano Y, Takeshita F, Nishimura S, Nonaka H, Chen YR, Sekine K, Kido T, Nakamura T, Kato S, Kanke T, Nakamura K, Nagai R, Ochiya T, Miyajima A
  • Journal Title: Proc Natl Acad Sci U S A Volume: 109 (11) Pages: 4263-4268
  • DOI: 10.1073/pnas.1117560109
  • Peer Reviewed
• [Journal Article] Regenerative medicine approach as an alternative treatment to islet transplantation (2012)
  • Author(s): Sekine K, Takebe T, Enomura M, Matsui C, Tanaka H, Taniguchi H
  • Journal Title: Transplant Proc Volume: 44(4) Pages: 1104-1106
  • DOI: 10.1016/j.transproceed.2012.03.020
  • Peer Reviewed
• [Journal Article] Highly efficient generation of definitive endoderm lineage from human induced pluripotent cells (2012)
  • Author(s): Sekine K, Takebe T, Suzuki Y, Kamiya A, Nakauchi H, Taniguchi H
  • Journal Title: Transplant Proc Volume: 44(4) Pages: 1127-1129
  • DOI: 10.1016/j.transproceed.2012.03.001
  • Peer Reviewed
• [Journal Article] Self-organization of human hepatic organoid by recapitulating organogenesis in vitro (2012)
  • Author(s): Takebe T, Sekine K, Suzuki Y, Enomura M, Tanaka S, Ueno Y, Zheng YW, Taniguchi H
  • Journal Title: Transplant Proc Volume: 44(4) Pages: 1018-1020
  • DOI: 10.1016/j.transproceed.2012.02.007
  • Peer Reviewed
• [Journal Article] Generation of human vascular network in vitro (2012)
  • Author(s): Takebe T, Koike N, Sekine K, Enomura M, Ueno Y, Zheng YW, Taniguchi H
  • Journal Title: Transplant Proc Volume: 44(4) Pages: 1130-1133
  • DOI: 10.1016/j.transproceed.2012.03.039
  • Peer Reviewed
• [Presentation] 膵癌幹細胞の系譜解析に向けたin vitroアッセイ系の構築 (2014)
  • Author(s): 久松大介、奥田諒、関根圭輔、上野康晴、谷口英樹
  • Organizer: 第13回日本再生医療学会総会
  • Place of Presentation: 京都
  • Year and Date: 20140304-06
• [Presentation] Pdx1陽性細胞は高い腫瘍形成能とスフィア形成能を有する癌幹細胞である (2013)
  • Author(s): 奥田諒、関根圭輔、孫略、坪井康次、谷口英樹
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 神奈川
  • Year and Date: 20131003-05
• [Presentation] 膵幹/前駆細胞の膵癌幹細胞への形質転換プロセスの解析 (2013)
  • Author(s): 関根圭輔、孫略、奥田諒、谷口英樹
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 神奈川
  • Year and Date: 20131003-05
• [Presentation] ヒト膵癌幹細胞における治療抵抗性機構の解析 (2013)
  • Author(s): 星野小百合、関根圭輔、孫略、中田晋、寺崎哲也、森永総一郎、宮城洋平、遠藤格、横瀬智之、倉田昌直、上野康晴、谷口英樹
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 神奈川
  • Year and Date: 20131003-05
• [Presentation] Targeted proteomic absolute quantification on transporters of human pancreatic cancer cells with gemcitabine-resistance (2013)
  • Author(s): Ueno Y, Hoshino S, Tsuchida N, Nakata S, Uchida Y, Sekine K, Zheng YW, Kurata M, Morinaga S, Miyagi Y, Yokose T, Endo I, Terasaki T, Hirano H, Taniguchi H
  • Organizer: HUPO 12th annual world congress
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 20130914-18
• [Presentation] Fluorescence visualizaiton of human induced pluripotent stem cells using transcription activator-like(TAL) effector nucleases (2013)
  • Author(s): Sekine K, Takebe T, Zhang R, Taniguchi H
  • Organizer: The 13th Congress of the Asian Society of Transplantation
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20130902-06
• [Presentation] 膵癌幹細胞のin vitroアッセイ系の解析 (2012)
  • Author(s): 奥田諒、孫略、関根圭輔、松井智栄美、坪井康次、谷口英樹
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 20121211-14
• [Presentation] 膵癌モデルマウスを用いた膵癌幹細胞の細胞系譜解析 (2012)
  • Author(s): 孫略、奥田諒、関根圭輔、盛武敬、坪井康次、谷口英樹
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 20120919-21
• [Presentation] 膵肝/前駆細胞の膵癌幹細胞への形質転換プロセスの解析 (2012)
  • Author(s): 関根圭輔、孫略、奥田諒、谷口英樹
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 20120919-21
• [Presentation] Identification of pancreatic stem/progenitor cells expressing PDX1 reside in the CD133 positive pancreatic duct (2012)
  • Author(s): Sekine K, Ishikawa M, Takebe T, Suzaki A, Kawashimo K, Matsui C, Taniguchi H
  • Organizer: International Society for Stem Cell Research 10^<th> annual meeting
  • Place of Presentation: Yokohama,Japan
  • Year and Date: 20120613-16