Epiblast pluripotency regulated by Nodal signal

• Project/Area Number: 23570233
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Kyushu University
• Principal Investigator: SUMI tomoyuki 九州大学, 医学(系)研究科(研究院), 研究員 (90378894)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 幹細胞 / エピブラスト / Wntシグナル / 発生・分化 / シグナル伝達

Research Abstract

Epiblast stem cells (EpiSCs) are primed pluripotent stem cells and can be derived from postimplantation mouse embryos. We now show that the absence of canonical Wnt/beta-catenin signaling is essential for maintenance of the undifferentiated state in mouse EpiSCs and in the epiblast of mouse embryos. Attenuation of Wnt signaling with the small-molecule inhibitor XAV939 or deletion of the beta-catenin gene blocked spontaneous differentiation of EpiSCs toward mesoderm and enhanced the expression of pluripotency factor genes, allowing propagation of EpiSCs as a homogeneous population. EpiSCs were efficiently established and propagated in the presence of both XAV939. Such an improvement in the homogeneity of pluripotency achieved with the use of a Wnt inhibitor should prove advantageous for manipulation of primed pluripotent stem cells.

Research Products

• [Journal Article] Wnt signaling regulates left-right axis formation in the node of mouse embryos (2013)
  • Author(s): Kitajima, Oki, Ohkawa, Sumi, Meno
  • Journal Title: Dev Biol Volume: 380 Issue: 2 Pages: 222-32
  • DOI: 10.1016/j.ydbio.2013.05.011
  • Peer Reviewed
• [Journal Article] Epiblast ground state is controlled by canonical Wnt/ β-catenin signaling in the postimplantation mouse embryo and epiblast stem cells (2013)
  • Author(s): Sumi, Oki, Kitajima, Meno
  • Journal Title: PLoS One Volume: 8 Issue: 5 Pages: e63378-e63378
  • DOI: 10.1371/journal.pone.0063378
  • Peer Reviewed
• [Journal Article] The SMAD2/3 corepressor SNON maintains pluripotency through selective repression of mesendodermal genes in human ES cells (2012)
  • Author(s): Tsuneyoshi N, Tan EK, Sadasivam A, Poobalan Y, Sumi T, Nakatsuji N, Suemori H, Dunn NR
  • Journal Title: Genes Dev Volume: Nov 15; 26(22) Issue: 22 Pages: 2471-6
  • DOI: 10.1101/gad.201772.112
  • Peer Reviewed
• [Journal Article] Simple and highly efficient method for production of endothelial cells from human embryonic stem cells (2011)
  • Author(s): Tatsumi R, Suzuki Y, Sumi T, Sone M, Suemori H, Nakatsuji N
  • Journal Title: Cell Transplant Volume: 20 Issue: 9 Pages: 1423-1430
  • DOI: 10.3727/096368910x547444
  • Peer Reviewed
• [Journal Article] Neurexin-1, a presynatic adhesion molecule, localizes at the slit diaphragm of the glomerular podocytes in kidneys (2011)
  • Author(s): Saito A, Miyauchi N, Hashimoto T, Karasawa T, Han GD, Kayaba M, Sumi T, Tomita M, Ikezumi Y, Suzuki K, Koitabashi Y, Shimizu F, Kawachi H
  • Journal Title: Am J Physiol Regulatory Integrative Comparative Physiology Volume: 300 Issue: 2 Pages: R340-R348
  • DOI: 10.1152/ajpregu.00640.2009
  • Peer Reviewed
• [Remarks]
  • URL: http://www.dev.med.kyushu-u.ac.jp/