Molecular mechanisms of the maintenance of stem cell systems

• Project/Area Number: 18390088
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Osaka University
• Principal Investigator: NAKANO Toru Osaka University, Graduate Schal of Frontier Biosziences, Professor (00172370)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥16,730,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥2,130,000); Fiscal Year 2007: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000); Fiscal Year 2006: ¥7,500,000 (Direct Cost: ¥7,500,000)
• Keywords: Stem cells / ES cells / Signal transduction / Blood cells / Cell differentiation / Reprogramming / Regenerative medicine

Research Abstract

To analyze the molecular mechanisms of the maintenance of stem cell immaturity and those of the cell differentiation in stem cell systems, we carried out the following research.
1) Function of Akt signal in the maintenance of embryonic stem cells
Nuclear reprogramming' can take place by cell fusion between somatic cells with mouse embryonic stem calls (ES cells). Activation of Akt signaling in ES cells significantly promoted the efficiency of the reprogramming. In addition, the cells obtained by the cell fusion acquired the pluripotency Them results clearly demonstrate that Akt signal can maintain the pluripotency of the cells. To the contrary, Akt signaling significantly reduced the efficiency of reprogramming after somatic nuclear transfer.
2) Reprogramming of blood cell differentiation by the null mutation of GATA-1
GATA-1 is an essential transcription factor for erythroid differentiation. In vitro differentiation from GATA-1 null ES cells to erythroid cells gave rim to the erythroid cells. And the erythroid nails mild proliferate for long term. These erythroid cells possessed the ability to differentiate to neutrophils and macrophages. In addition, epigenetic status of the GATA-1 null erythroid cells was quite different from its wild type counterpart. This result clearly demonstrate that this experimental system is an excellent model system to analyze the epigenetic modification by transcription factors.

Research Products

• [Journal Article] Akt signaling promotes derivation of embryonic germ cells from primordial germcells (2008)
  • Author(s): Kimura T, Tomooka M, Yamano N, 3名, Kanai Y, Nakano T
  • Journal Title: Development 135 Pages: 866-879
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Differential context-dependent effects of FOG-1 on mast cell development and differentiation (2008)
  • Author(s): Sugiyama D, Tanaka M, Kitajima K, 3名, Yamatodani A, Nakano T
  • Journal Title: Blood 111 Pages: 1924-1932
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Akt signaling promotes derivation of embryonic germ cells from primordial germ cells (2008)
  • Author(s): Kimura, T, Tomooka, M, Yamano, N, Murayama, K, Matoba, S, Umehara, H, Kanai, Y, Nakano,_T
  • Journal Title: Development 135 Pages: 869-79
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Differential context-dependent effects of FOG-1 on mast cell development and differentiation (2008)
  • Author(s): Sugiyama, D, Tanaka, M, Kitajima, K, Zheng, J, Yen, H, Murotani, T, Yamatodani, A, Nakano, T
  • Journal Title: Blood 111 Pages: 1924-32
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Akt signaling promotes derivation of embryonic germ cells from primordial germ cells (2008)
  • Author(s): Kimura T, Tomooka M, Yamano N, 3名, Kanai Y, Nakano T
  • Journal Title: Development (In press)
• [Journal Article] Differential context-dependent effects of FOG-1 on mast cell development and differentiation (2008)
  • Author(s): Sugiyama D, Tanaka M, Kitajima K, 3名, Yamatodani A, Nakano T
  • Journal Title: Blood (In press)
• [Journal Article] PGC7/Stella protects against DNA demethylation in early embryogenesis (2007)
  • Author(s): Nakamura T, Arai Y, Umehara H, 8名, Shiota K, Nakano T
  • Journal Title: Nature Cell Biology 9 Pages: 64-71
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Akt activation induces epidermal hyperplasia and proliferation of epidermal progenitors (2007)
  • Author(s): Murayama K, Kimura T, Tarutani M, 5名, Katayama I, Nakano T
  • Journal Title: Oncogene 26 Pages: 4882-4888
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Pten/PI3K pathway governs the homeostasis of Valpha14iNKT cells (2007)
  • Author(s): Kishimoto H, Ohteki T, 11名, Nakano T, Koyasu S, Sasaki T, Suzuki
  • Journal Title: Blood 109 Pages: 3316-3324
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Efficient derivation of embryonic stem cells by inhibition of glycogen synthase kinase-3 (2007)
  • Author(s): Umehara H, Kimura T, Ohtsuka S, 4名, Niwa H, Nakano T
  • Journal Title: Stem Cells 25 Pages: 2705-2711
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] PGC7/Stella protects against DNA demethylation in early embryogenesis (2007)
  • Author(s): Nakamura, T, Arai, Y, Umehara, H, Masuhara, M, Kimura, T, Taniguchi, H, Sekimoto, T, Ikawa, M, Yoneda, Y, Okabe, M, Tanaka, S, Shiota, K, Nakano, T
  • Journal Title: Nature Cell Biol 9 Pages: 64-71
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Akt activation induces epidermal hyperplasia and proliferation of epiderthal progenitors (2007)
  • Author(s): Murayama, K, Kimura, T, Tarutani, M, Tomooka, M, Hayashi, R, Okabe, M, Nishida, K, Itami, S, Katavama, I, Nakano, T
  • Journal Title: Oncogene 26 Pages: 4882-8
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Pten/PI3K pathway governs the homeostasis of Valphal4iNKT cells (2007)
  • Author(s): Kishimoto, H, Ohteki, T, Yajima, N, Kawahara, K, Natsui, M, Kawarasaki, S, Hamada, K, Horie, Y, Kubo, Y, Arase, S, Taniguchi, M, Vanhaesebroeck, B, Mak, TW., Nakano, T., Kovasu, S., Sasaki, T., Suzuki
  • Journal Title: Blood 109 Pages: 3316-24
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Efficient derivation of embryonic stem cells by inhibition of glycogen synthase kinase-3 (2007)
  • Author(s): Umehara, H, Kimura, T, Ohtsuka, S, Nakamura, T, Kitajima, K, Ikawa, M, Okabe, M, Niwa, H, Nakano, T
  • Journal Title: Stem Cells 25 Pages: 2705-11
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] PGC7/Stella protects against DNA demethylation in early embryogenesis (2007)
  • Author(s): Nakamura T, Arai Y, Umehara H, 8名, Shiota K, Nakano T
  • Journal Title: Nature Cell Biol 9 Pages: 64-71
• [Journal Article] Pten/PI3K pathway governs the homeostasis of Valphal4iNKT cells (2007)
  • Author(s): Kishimoto H, Ohteki T, 11名, Nakano T, Koyasu S, Sasaki T, Suzuki
  • Journal Title: Blood 109 Pages: 3316-3324
• [Journal Article] Efficient derivation of embryonic stem cells by inhibition of glycogen synthase kinase-3 (2007)
  • Author(s): Umehara H, Kimura T, Ohsuka S, 4名, Niwa H, Nakano T
  • Journal Title: Stem Cells 25 Pages: 2705-2711
• [Journal Article] Differential Effects of GATA-1 on Proliferation and Differentiation of Erythroid Lineage Cells (2006)
  • Author(s): Zheng J, Kitajima K, Sakai E, Kimura T, Minegishi N, Yamamoto M, Nakano T
  • Journal Title: Blood 107 Pages: 520-527
• [Journal Article] Activation of Akt Signaling is Sufficient to Maintain Pluripotency in Mouse and Primate Embryonic Stem Cells (2006)
  • Author(s): Watanabe S, Umehara H, Murayama K, Okabe M, Kimura T, Nakano T
  • Journal Title: Oncogene 25 Pages: 2697-2707
• [Journal Article] Redirecting Differentiation of Hematopoietic Progenitors by a Transcription Factor GATA-2 (2006)
  • Author(s): Kitajima K, Tanaka M, Yen H, Sato A, Umehara H, Sakai E, Nakano T
  • Journal Title: Blood 107 Pages: 1857-1863
• [Journal Article] Multipotential differentiation ability of GATA-1 null erythroid committed cells (2006)
  • Author(s): Kitajima K, Zheng J, Yen H, Sugiyama D, Nakano T
  • Journal Title: Genes ＆ Development 20 Pages: 654-659
• [Journal Article] A novel class of small RNAs bind to MILI protein in mouse testes (2006)
  • Author(s): Aravin A, Gaidatzis D, (8名), Nakano T, (6名), Tuschl T
  • Journal Title: Nature 442 Pages: 203-207
• [Journal Article] Characterization of the piRNA complex from rat testes (2006)
  • Author(s): Lau NC, (3名), Nakano T, Bartel DP, Kingston RE
  • Journal Title: Science 313 Pages: 363-367
• [Presentation] Analyzing the function of GATA-1 and its related factors by in vitro differentiation of mouse ES cells (2007)
  • Author(s): Toru Nakano
  • Organizer: EMBO Workshop on GATA Factors
  • Place of Presentation: カプリ島、イタリア
  • Year and Date: 2007-04-15
  • Description: 「研究成果報告書概要(和文)」より