Biological characterization of hematopoietic stem cells and leukemic cells by monitoring ESAM expression

• Project/Area Number: 24591423
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Osaka University
• Principal Investigator: YOKOTA Takafumi 大阪大学, 医学(系)研究科(研究院), 助教 (60403200)
• Co-Investigator(Kenkyū-buntansha): ORITANI Kenji 大阪大学, 大学院医学系研究科, 准教授 (70324762) ; KANAKURA Yuzuru 大阪大学, 大学院医学系研究科, 教授 (20177489)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 造血幹細胞 / 白血病 / ヒト白血病 / ヒト白血病の診断

Outline of Final Research Achievements

Hematopoietic stem cells (HSCs) have potencies for differentiation and self-renewal to supply blood cells throughout life. In homeostasis, most HSCs exist in a quiescent state. However, they immediately proliferate in response to myelosuppression. In this study, we have shown that monitoring of endothelial cell-selective adhesion molecule (ESAM) level is useful to indicate HSC activation in mice. ESAM levels clearly mirrored the shift of HSCs between quiescence and activation, and it was prominent in comparison to other HSC markers.
Although human HSCs are of great value in treatment for hematopoietic diseases and in regenerative medicine, studies for their nature are hampered by a paucity of information about their precise immunophenotype. This is in stark contrast to the mouse, which is much more characterized in this regard. In this study we report that ESAM is a robust marker of human HSCs, and is also found specifically on an aggressive subset of leukaemia cell lines.

Research Products

• [Journal Article] Estrogen-inducible sFRP5 inhibits early B-lymphopoiesis in vivo, but not during pregnancy (2015)
  • Author(s): Takafumi Yokota, Kenji Oritani, Takao Sudo, Tomohiko Ishibashi1, Yukiko Doi, Yoko Habuchi, Michiko Ichii, Kentaro Fukushima, Daisuke Okuzaki, Kazuma Tomizuka, Kengo Yamawaki, Makoto Kakitani, Akihiko Shimono, Eiichi Morii, Paul W. Kincade, Yuzuru Kanakura
  • Journal Title: European Journal of Immunology Volume: in press Issue: 5 Pages: 1390-1401
  • DOI: 10.1002/eji.201444939
  • Peer Reviewed / Open Access
• [Journal Article] Guest editorial: Molecular mechanisms of lymphocyte development: recent findings (2014)
  • Author(s): Takafumi Yokota
  • Journal Title: International Journal of Hematology Volume: 100 Issue: 3 Pages: 218-219
  • DOI: 10.1007/s12185-014-1645-4
  • Open Access
• [Journal Article] Role of tissue-specific AT-rich DNA sequence-binding proteins in lymphocyte differentiation (2014)
  • Author(s): Takafumi Yokota, Yuzuru Kanakura
  • Journal Title: International Journal of Hematology Volume: 100 Issue: 3 Pages: 238-245
  • DOI: 10.1007/s12185-014-1602-2
  • Peer Reviewed / Open Access
• [Journal Article] Markers for Hematopoietic Stem Cells: Histories and Recent Achievements (2012)
  • Author(s): Yokota T, Oritani K, Butz S, Ewers S, Vestweber D, Kanakura Y.
  • Journal Title: Advances in Hematopoietic Stem Cell Research Volume: 1 Pages: 77-88
  • Peer Reviewed
• [Journal Article] The endothelial antigen ESAM monitors hematopoietic stem cell status between quiescence and self-renewal. (2012)
  • Author(s): Sudo T, Yokota T, Oritani K, Satoh Y, Sugiyama T, Ishida T, Shibayama H, Ezoe S, Fujita N, Tanaka H, Maeda T, Nagasawa T, Kanakura Y.
  • Journal Title: The Journal of Immunology Volume: 189 Pages: 200-210
  • Peer Reviewed
• [Presentation] MS4A3 Marks Early Myeloid Differentiation in Human Hematopoiesis (2014)
  • Author(s): Tomohiko Ishibashi, Takafumi Yokota, Yusuke Satoh, Takao Sudo, Yukiko Doi, Natsuko Fujita, Yasuhiro Nagate, Yuri Hamanaka, Keiko Matsui, Akira Tanimura, Michiko Ichii, Norimitsu Saitoh, Sachiko Ezoe, Hirohiko Shibayama, Kenji Oritani, Yuzuru Kanakura
  • Organizer: American Society of Hematology
  • Place of Presentation: San Francisco (USA)
  • Year and Date: 2014-12-08
• [Presentation] ESAM on hematopoietic cells is essential for recovery of erythropoiesis after bone marrow injury (2014)
  • Author(s): Takao Sudo, Takafumi Yokota, Daisuke Okuzaki, Michiko Ichii, Tomohiko Ishibashi, Tomomi Isono, Yukiko Doi, Masako Takemoto, Yoko Habuchi, Akira Tanimura, Sachiko Ezoe, Hirohiko Shibayama, Kenji Oritani, Yuzuru Kanakura
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪国際会議場（ 大阪市 ）
  • Year and Date: 2014-11-01
• [Presentation] Functional analysis of a chromatin-remodeling protein in early lymphoid differentiation (2014)
  • Author(s): Yukiko Doi, Takafumi Yokota, Akira Tanimura, Norimitsu Saitoh, Michiko Ichii, Sachiko Ezoe, Hirohiko Shibayama, Kenji Oritani, Yuzuru Kanakura
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪国際会議場（ 大阪市 ）
  • Year and Date: 2014-11-01
• [Presentation] Endothelial antigen ESAM marks human hematopoietic stem/progenitor cells in diverse sources (2014)
  • Author(s): Tomohiko Ishibashi, Takafumi Yokota, Michiko Ichii, Takao Sudo, Yukiko Doi, Natsuko Fujita, Yasuhiro Nagate, Yuri Hamanaka, Keiko Matsui, Akira Tanimura, Norimitsu Saitoh, Sachiko Ezoe, Hirohiko Shibayama, Kenji Oritani, Yuzuru Kanakura
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪国際会議場（ 大阪市 ）
  • Year and Date: 2014-10-31
• [Presentation] A new HSC marker ESAM is necessary for erythroid cell recovery after bone marrow injury
  • Author(s): Takao Sudo, Takafumi Yokota, Kenji Oritani, Michiko Ichii, Tomohiko Ishibashi, Natsuko Fujita, Yuzuru Kanakura
  • Organizer: 日本血液学会
  • Place of Presentation: ロイトン札幌、札幌、北海道
• [Presentation] Endothelial Cell-Selective Adhesion Molecule Marks Human Hematopoietic Stem Cells Regardless Of The HSC Sources
  • Author(s): Tomohiko Ishibashi, Takafumi Yokota, Michiko Ichii, Yusuke Satoh, Takao Sudo, Satoko Fujita, Yukiko Doi, Natsuko Fujita, Yasuhiro Nagate, Yuri Hamanaka, Keiko Matsui, Akira Tanimura, Norimitsu Saitoh, Sachiko Ezoe, Hirohiko Shibayama, Paul W. Kincade, Kenji Oritani, Yuzuru Kanakura
  • Organizer: 米国血液学会
  • Place of Presentation: Ernest N. Morial Convention Center, New Orleans, LA, USA
• [Presentation] Role of endothelial antigen ESAM in hematopoietic stem cells status
  • Author(s): Sudo T, Yokota T, Oritani K, Satoh Y, Sugiyama T, Ishida T, Shibayama H, Ezoe S, Ichii M, Tanimura A, Fujita N, Ishibashi T, Matsui K, Hamanaka Y, Nagasawa T, Kanakura Y
  • Organizer: 第74回日本血液学会総会
  • Place of Presentation: 京都 国立京都国際会館
• [Presentation] Significance of novel HSC marker ESAM expression in cord blood
  • Author(s): Ishibashi T, Yokota T, Satoh Y, Sudo T, Ichii M, Shibayama H, Ezoe S, Tanimura A, Fujita N, Matsui K, Hamanaka Y, Oritani K, Kanakura Y
  • Organizer: 第74回日本血液学会総会
  • Place of Presentation: 京都 国立京都国際会館
• [Presentation] The endothelial antigen ESAM level distinguishes HSC status between quiescence and self-renewal
  • Author(s): Sudo T, Yokota T, Oritani K, Satoh Y, Sugiyama T, Nagasawa T, Kanakura Y
  • Organizer: 第41回日本免疫学会総会
  • Place of Presentation: 神戸 神戸国際会議場
• [Book] Annual Review 血液 2015 (2015)
  • Author(s): 横田貴史
  • Total Pages: 18
  • Publisher: 中外医学社