The role of SATB1-MS4A3 in the differentiation of hematopoietic stem cells

• Project/Area Number: 26461412
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kobe Shoin Women's University
• Principal Investigator: SATOH YUSUKE 神戸松蔭女子学院大学, 人間科学部, 准教授 (20506307)
• Co-Investigator(Kenkyū-buntansha): 石橋 知彦 国立研究開発法人国立循環器病研究センター, 研究所, 研究員 (30722285) ; 横田 貴史 大阪大学, 医学系研究科, 助教 (60403200) ; 織谷 健司 大阪大学, 医学系研究科, 准教授 (70324762)
• Co-Investigator(Renkei-kenkyūsha): TANAKA HIROKAZU 近畿大学, 医学部, 講師 (40360846)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 造血幹細胞 / SATB1 / MS4A3 / 血球分化

Outline of Final Research Achievements

We generated hematological-lineage restricted SATB1 conditional knock out (cKO) mice. Analyzing the adult bone marrow (BM) in these mice, we observed a significant decrease in the number of HSCs as compared to those in their wild type (WT) littermates. SATB1 cKO mice-derived HSCs showed lower BM reconstitution ability than WT HSCs. Next, we generated SATB1 reporter mice, and examined the early differentiation of HSCs. We found that the HSC fraction of adult BM consists of SATB1－ and SATB1+ cells. In transplantation experiments, the SATB1+ HSCs produced more lymphocytic cells and fewer myeloid cells in the recipients.
The membrane protein MS4A3 is negatively regulated by SATB1, and we found that MS4A3 expression was observed in primary acute myeloid leukemia cases. In addition , a MS4A3 antibody induced complement-dependent cell death in several human AML lines. These results suggest that MS4A3 may serve as a putative therapeutic target to treat myeloid malignancies.

Research Products

• [Journal Article] ESAM is a novel human hematopoietic stem cell marker associated with a subset of human leukemias. (2016)
  • Author(s): Ishibashi T, Yokota T, Tanaka H, Ichii M, Sudo T, Satoh Y, Doi Y, Ueda T, Tanimura A, Hamanaka Y, Ezoe S, Shibayama H, Oritani K, Kanakura Y.
  • Journal Title: Experimental Hematology Volume: 44 Issue: 4 Pages: 269-281
  • DOI: 10.1016/j.exphem.2015.12.010
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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] Identification of osteoblast stimulating factor 5 as a negative regulator in the B-lymphopoietic niche. (2015)
  • Author(s): Fujita N, Ichii M, Maeda T, Saitoh N, Yokota T, Yamawaki K, Kakitani M, Tomizuka K, Oritani K, Kanakura Y
  • Journal Title: Experimental Hematology Volume: 43 Issue: 11 Pages: 963-973
  • DOI: 10.1016/j.exphem.2015.07.002
  • Peer Reviewed
• [Journal Article] The anti-apoptotic gene Anamorsin is essential for both autonomous and extrinsic regulation of murine fetal liver hematopoiesis. (2014)
  • Author(s): Tanimura A, Shibayama H, Hamanaka Y, Fujita N, Ishibashi T, Sudo T, Yokota T, Ezoe S, Tanaka H, Matsumura I, Oritani K, Kanakura Y.
  • Journal Title: Exp Hematol. Volume: 42 Issue: 5 Pages: 410-422
  • DOI: 10.1016/j.exphem.2014.01.002
  • Peer Reviewed / Open Access
• [Journal Article] Clathrin assembly protein CALM Plays a Critical Role in KIT Signaling by Regulating Its Cellular Transport from Early to Late Endosomes in Hematopoietic Cells. (2014)
  • Author(s): Shinya Rai, Hirokazu Tanaka*, Mai Suzuki , Honami Ogoh, Yasuhiro Taniguchi, Yasuyoshi Morita, Takahiro Shimada, Akira Tanimura, Keiko Matsui, Takafumi Yokota, Kenji Oritani, Kenji Tanabe, Toshio Watanabe, Yuzuru Kanakura, and Itaru Matsumura
  • Journal Title: PLoS ONE Volume: 該当しない Issue: 10 Pages: 0109441-0109441
  • DOI: 10.1371/journal.pone.0109441
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Signal-transducing adaptor protein-2 regulates macrophage migration into inflammatory sites during dextran sodium sulfate induced colitis. (2014)
  • Author(s): Fujita N, Oritani K, Ichii M, Yokota T, Saitoh N, Okuzaki D, Sekine Y, Kon S, Muromoto R, Saitoh K, Yoshimura A, Matsuda T, Kanakura Y.
  • Journal Title: Eur J Immunol. Volume: 44 Issue: 6 Pages: 1791-1801
  • DOI: 10.1002/eji.201344239
  • Peer Reviewed / Open Access
• [Presentation] SATB1 expression helps in identification of the lymphoid-lineage-biased trajectory of functionally fluctuating hematopoietic stem cells (2016)
  • Author(s): Yukiko Doi, Takafumi Yokota, Yusuke Satoh, Tomoaki Ueda, Yasuhiro Shingai, Michiko Ichii, Akira Tanimura, Sachiko Ezoe, Hirohiko Shibayama, Kenji Oritani, Terumi Kohwi-Shigematsu, Yuzuru Kanakura
  • Organizer: 第58回米国血液学会
  • Place of Presentation: サンディエゴ
  • Year and Date: 2016-12-03
  • Int'l Joint Research
• [Presentation] SATB1 expression marks lymphoid-lineage-biased hematopoietic stem cells in mouse bone marrow (2016)
  • Author(s): 横田 貴史, 石橋 知彦, 佐藤 友亮, 一井 倫子, 谷村 朗, 江副 幸子, 柴山 浩彦, 織谷 健司, 金倉 譲
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-13
• [Presentation] SATB1 Expression Marks Lymphoid-Lineage-Biased Hematopoietic Stem Cells in Mouse Bone Marrow. (2015)
  • Author(s): Doi Y, Yokota T, Ishibashi T, Satoh Y, Ichii M, Tanimura A, Ezoe S, Shibayama H, Oritani K, Kanakura Y.
  • Organizer: 57th ASH Annual Meeting and Exposition.
  • Place of Presentation: Orlando, FL
  • Year and Date: 2015-12-05
  • Int'l Joint Research
• [Presentation] ESAM Is a Novel Human Hematopoietic Stem Cell Marker Associated with a Subset of Human Leukemias (2015)
  • Author(s): Ishibashi T, Yokota T, Tanaka H, Ichii M, Sudo T, Satoh Y, Doi Y, Tanimura A, Hamanaka Y, Ezoe S, Shibayama H, Oritani K, Kanakura Y.
  • Organizer: 57th ASH Annual Meeting and Exposition.
  • Place of Presentation: Orlando, FL
  • Year and Date: 2015-12-05
  • Int'l Joint Research
• [Presentation] MS4A3-Marks-Early-Myeloid-Differen>a>on-in-Human-Hematopoiesis. (2014)
  • Author(s): Ishibashi T, Yokota T, Satoh Y, Sudo T, Doi Y, Fujita N, Nagate Y, Hamanaka Y, Matsui K, Tanimura A, Ichii M, Saitoh N, Ezoe S, Shibayama H, Oritani K, Kanakura Y.
  • Organizer: 56th ASH Annual Meeting and Exposition.
  • Place of Presentation: San Francisco, CA
  • Year and Date: 2014-12-06 – 2014-12-09