Molecular mechanisms of self-renewal of hepatic stem/progenitor cells during liver development and hepatic tumorigenesis

2012 Fiscal Year Final Research Report

• Project/Area Number: 23791490
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Yokohama City University
• Principal Investigator: UENO Yasuharu 横浜市立大学, 医学部, 助教 (60375235)
• Project Period (FY): 2011 – 2012
• Keywords: 組織幹細胞 / 自己複製 / ポリコーム群タンパク質

Research Abstract

To elucidate the molecular mechanism of hepatic tumorigenesis, which is considered to related to the self-renewal of hepatic stem/progenitor cell, we attempted to identify the downstream target genes of Polycomb group protein Ring1 that is essential for self-renewal of hepatic stem cells. By microarray and ChIP-PCR analysis, we extracted Cdkn2a as a Ring1B target gene. We investigated the expansion of hepatic stem/progenitor cell during hepatogenesis in cdkn2a and ring1B deficient mice, the result showed that the rescue is limited. We concluded that Ring1B should have other important downstream targets in addition to Cdkn2a in stem/progenitor cells.

Research Products

• [Journal Article] The generation of pancreatic beta-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, Taniguchi H.
  • Journal Title: Biomaterials Volume: 34(23) Pages: 5785-9
  • Peer Reviewed
• [Journal Article] Establishment of automated culture system for murine induced pluripotent stem cells (2012)
  • Author(s): Koike H, Kubota K, Sekine K, Takebe T, Ouchi R, Zheng YW, Ueno Y, Tanigawa N, Taniguchi H.
  • Journal Title: nt stem cells. BMC biotechnology Volume: 12(1) Pages: 81
  • 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
  • Peer Reviewed
• [Journal Article] Generation of human vascular network in vitro (2012)
  • Author(s): Takebe T, Koike N, Sekine K, Enomura M, Chiba Y, Ueno Y, Zheng YW, Taniguchi H.
  • Journal Title: ransplant Proc Volume: 44(4) Pages: 1130-1133
  • Peer Reviewed
• [Journal Article] Reconstitution of hepatic tissue architectures from fetal liver cells obtained from a three-dimensional culture with arotating wall vessel bioreactor (2011)
  • Author(s): Ishikawa M, Sekine K, Okamura A, Zheng YW, UenoY, Koike N, Tanaka J, Taniguchi H.
  • Journal Title: essel bioreactor. J Biosci Bioeng Volume: 111 Pages: 711-718
  • Peer Reviewed
• [Journal Article] ascularized and functional human liver from an iPSC-derived organ bud transplant
  • 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: (in print)
  • Peer Reviewed
• [Presentation] Quantitative targeted absolute proteomics of transporters in the pancreatic cancer treated with neoadjuvant chemoradiation therapy (2012)
  • Author(s): Ueno Y, Sun L, Ouchi R, Nakata S, Zheng YW, Terasaki T, Kurata M, Yamamoto N, Morinaga S, Miyagi Y, Yokose T, Endo I, Taniguchi H.
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌市教育文化会館(北海道)
  • Year and Date: 20120919-21
• [Presentation] Polycomb group protein Ezh2 regulates the expansion of murine hepatic stem/progenitor cells (2012)
  • Author(s): Ouchi R, Ueno Y, Koike H, Yuta O, Isono K, Koseki H, Taniguchi H
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌市教育文化会館(北海道)
  • Year and Date: 20120919-21
• [Presentation] Polycomb group protein Ring1B regulates proliferation and differentiation of mouse hepatic stem/ progenitor cell by repressing cyclin-dependent kinase inhibitors (2012)
  • Author(s): Koike H, Ueno Y, Naito T, Shina T, Ouchi R, Isono K, Koseki H, Taniguchi H
  • Organizer: International Society for Stem Cell Research 10th annual meeting.
  • Place of Presentation: Yokohama,Japan, Pacifico Yokohama(KANAGAWA)
  • Year and Date: 20120613-16
• [Presentation] Role of the polycomb group protein EZH2 in the murine hepatic stem/progenitor cells (2012)
  • Author(s): Ouchi R, Ueno Y, Koike H, Shiina T, Obana Y, Isono K, Koseki H, Taniguchi H
  • Organizer: International Society for Stem Cell Research 10th annual meeting
  • Place of Presentation: Yokohama,Japan, Pacifico Yokohama(KANAGAWA)
  • Year and Date: 20120613-16
• [Presentation] Self-renewal versus differentiation as well as the liver repopulation capability of human hepatic stem cells (2012)
  • Author(s): Zheng Y, Li B, Zhang R, Kimura M, Tsuchida T, Takebe T, Ueno Y, Sekine K, Taniguchi H
  • Organizer: International Society for Stem Cell Research 10th annual meeting
  • Place of Presentation: Yokohama,Japan, Pacifico Yokohama(KANAGAWA)
  • Year and Date: 20120613-16
• [Presentation] Construction of chimeric mice with human immatured hepatocytes (2012)
  • Author(s): Zhang R, Zheng Y, Tsuchida T, Takebe T, Kimura M, Li B, Takiguchi K, Sekine K, Ueno Y, Taniguchi H
  • Organizer: International Society for Stem Cell Research 10th annual meeting
  • Place of Presentation: Yokohama,Japan, Pacifico Yokohama(KANAGAWA)
  • Year and Date: 20120613-16
• [Presentation] Creation of vascularized human organ from induced pluripotent stem cells (2012)
  • Author(s): Takebe T, Sekine K, Enomura M, Suzuki Y, Koike H, Zhang R, Koike N, Ueno Y, Zheng Y, Taniguchi H
  • Organizer: International Society for Stem Cell Research 10th annual meeting
  • Place of Presentation: Yokohama,Japan, Pacifico Yokohama(KANAGAWA)
  • Year and Date: 20120613-16
• [Presentation] 多能性幹細胞を用いた機能的なヒト臓器の創出 (2012)
  • Author(s): 武部貴則、関根圭輔、江野村允宏、小池博之、張冉冉、三橋優澄、上野康晴、鄭允文、谷口英樹
  • Organizer: 第11回日本再生医療学会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 20120612-14
• [Presentation] Ring1B Regulates Proliferation of Hepatic Stem/Progenitor Cells by Repressing Cyclin-dependent Kinase Inhibitors (2011)
  • Author(s): Koike H, Ueno Y, Shiina T, Naito T, Ouchi R, Isono K, Koseki H, Taniguchi H.
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2011-12-13
• [Presentation] The functional analysis of polycomb group protein Ezh2 in the self-renewal of the fetal mouse hepatic stem/progenitor cell (2011)
  • Author(s): Ouchi R, Ueno Y, Koike H, Obana Y, Isono K, Koseki H, Taniguchi H.
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2011-12-13
• [Presentation] In vitroでの自己組織化肝オルガノイド形成 (2011)
  • Author(s): 武部貴則, 関根圭輔, 江野村允宏, 上野康晴, 鄭允文, 谷口英樹
  • Organizer: 第47回日本移植学会総会
  • Place of Presentation: 仙台国際センター (宮城)
  • Year and Date: 2011-10-05
• [Remarks]
  • URL: http://www-user.yokohama-cu.ac.jp/~saisei/