Role of bone marrow niche in human early lymphopoiesis

• Project/Area Number: 25461447
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Mie University
• Principal Investigator: Ohishi Kohshi 三重大学, 医学部附属病院, 准教授 (00397506)
• Co-Investigator(Kenkyū-buntansha): Tawara Isao 三重大学, 医学部附属病院, 助教 (80378380)
• Co-Investigator(Renkei-kenkyūsha): Nosaka Tetsuya 三重大学, 医学系研究科, 教授 (30218309)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ストローマ細胞 / SDF-1 / LFA-1 / リンパ球分化 / リンパ球系細胞分化

Outline of Final Research Achievements

By using coculture system with telomerized human bone marrow stromal cells, we found that stromal cell-derived factor 1 (SDF-1) is critical for stromal cell contact-induced early T- and B-lymphoid differentiation from human hematopoietic precursors but dispensable for early T-cell generation without contact with stromal cells and that LFA-1-mediated interaction with stromal cells is important for early T-lymphoid differentiation.

Research Products

• [Journal Article] A novel FOXP1-PDGFRA fusion gene in myeloproliferative neoplasm with eosinophilia (2015)
  • Author(s): Sugimoto Y, Sada A, Shimokariya Y, Monma F, Ohishi K, Masuya M, Nobori T, Matsui T, Katayama N
  • Journal Title: Cancer Genet Volume: 208 Issue: 10 Pages: 508-512
  • DOI: 10.1016/j.cancergen.2015.07.001
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Adoptive transfer of MAGE-A4 T-cell receptor gene-transduced lymphocytes in patients with recurrent esophageal cancer (2015)
  • Author(s): Kageyama S, Ikeda H, Miyahara Y, Imai N, Ishihara M, Saito K, Sugino S, Ueda S, Ishikawa T, Kokura S, Naota H, Ohishi K, Shiraishi T, Inoue N, Tanabe M, Kidokoro T, Yoshioka H, Tomura D, Nukaya I, Mineno J, Takesako K, Katayama N, Shiku H.
  • Journal Title: Clinical Cancer Research Volume: in press Issue: 10 Pages: 2268-2277
  • DOI: 10.1158/1078-0432.ccr-14-1559
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Histone deacetylase inhibition regulates inflammation and enhances Tregs after allogeneic hematopoietic cell transplantation in humans (2015)
  • Author(s): ③Choi SW, Gatza E, Hou G, Sun Y, Whitfield J, Song Y, Oravecz-Wilson K, Tawara I, Dinarello CA, Reddy P
  • Journal Title: Blood Volume: 125 Issue: 5 Pages: 815-819
  • DOI: 10.1182/blood-2014-10-605238
  • Peer Reviewed
• [Journal Article] ST2 blockade reduces sST2-producing T cells while maintaining protective mST2-expressing T cells during graft-versus-host disease (2015)
  • Author(s): Zhang J, Ramadan AM, Griesenauer B, Li W, Turner MJ, Liu C, Kapur R, Hanenberg H, Blazar BR, Tawara I, Paczesny S
  • Journal Title: Sci Transl Med Volume: 7 Issue: 308
  • DOI: 10.1126/scitranslmed.aab0166
  • Peer Reviewed
• [Journal Article] Monocytes infiltrate the pancreas via the MCP-1/CCR2 pathway and differentiate into stellate cells. (2014)
  • Author(s): Ino K, Masuya M, Tawara I, Miyata E, Oda K, Nakamori Y, Suzuki K, Ohishi K, Katayama N.
  • Journal Title: PLoS One Volume: 9 Issue: 1 Pages: 1-12
  • DOI: 10.1371/journal.pone.0084889
  • Peer Reviewed
• [Journal Article] Manipulation of human early T lymphopoiesis by coculture on human bone marrow stromal cells: Potential utility for adoptive immunotherapy (2013)
  • Author(s): Liu B, Ohishi K, Orito Y,N a k a mo r i Y, Nishikawa H, Ino K,Suzuki K, Matsumoto T,Masuya M,Hamada H, Mineno J, Ono R, Nosaka T, Shiku H, Katayama N.
  • Journal Title: Exp Hematol Volume: - Issue: 4 Pages: 367-376
  • DOI: 10.1016/j.exphem.2012.12.001
  • Peer Reviewed
• [Presentation] LFA-1-Mediated Adhesion to ICAM-2 Is Critical for Stromal Cell-Dependent Early T-Lymphoid Differentiation from Human Hematopoietic Precursors (2015)
  • Author(s): Hirohito Minami,Kohshi Ohishi, Masahiro Masuya, Naoyuki Katayama
  • Organizer: 57th American Society of Hematology Annual Meeting
  • Place of Presentation: Orlando, Florida, USA
  • Year and Date: 2015-12-05
  • Int'l Joint Research
• [Presentation] SDF-1 is involved in human early B- and T/NK-lineage lymphoid differentiation in a different manner (2015)
  • Author(s): Hirohito Minami, Kohshi Ohishi, Masahiro Masuya, Naoyuki Katayama
  • Organizer: 第77回 日本血液学会
  • Place of Presentation: 金沢
  • Year and Date: 2015-10-16
• [Presentation] Stromal cell-derived factor-1 plays important roles in the regulation of human early B- and T/NK-lineage lymphoid differentaition in different manners (2015)
  • Author(s): Hirohito Minami, Kohshi Ohishi, Masahiro Masuya, Naoyuki Katayama
  • Organizer: 20th European Hematology Association
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2015-06-11
  • Int'l Joint Research
• [Presentation] Important role for LFA-1 in early stage of human T lymphopoiesis (2014)
  • Author(s): Minami F, Ohishi K, Nakamori Y, Masuya M, Katayama N
  • Organizer: 日本血液学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] LFA-1-Mediated Adhesion Of Human Hematopoietic Progenitors To Bone Marrow Stromal Cells Enhances B-Lineage Differentiation Toward CD19+ ProB Cells, While The Generation Of CD7+CD56-CD45RA+ Multipotent Lymphoid and CD10+CD19- B-Biased Progenitors Is Supported By Soluble Factors Produced From Stromal Cells (2013)
  • Author(s): Minami H, Ohishi K, Nakamori Y, Masuya M, Katayama N
  • Organizer: 55th ASH Annual Meeting and Exposition
  • Place of Presentation: New Orleans, USA
• [Presentation] ROLE OF BONE MARROW STROMAL CELLS IN THE REGULATION OF HUMAN EARLY LYMPHOPOIESIS (2013)
  • Author(s): Ohishi K, Nakamori Y, Katayama N
  • Organizer: The 18th Congress of European Hematology Association
  • Place of Presentation: Stockholm, Sweden
  • Invited
• [Presentation] ヒトリンパ球の初期分化制御におけるヒト骨髄ストローマ細胞の役割 (2013)
  • Author(s): 南 博仁, 大石 晃嗣, 中森 良樹, 鈴木 圭, 桝屋 正浩, 片山 直之
  • Organizer: 第７５回日本血液学会総会
  • Place of Presentation: さっぽろ芸文館
  • Invited
• [Presentation] ヒトB・Tリンパ球系細胞初期分化におけるヒトストローマ細胞の役割 (2013)
  • Author(s): 大石晃嗣、片山直之
  • Organizer: 第７２回日本癌学会総会
  • Place of Presentation: パシフィコ横浜
  • Invited
• [Book] 血液内科 (2013)
  • Author(s): 大石晃嗣、門間文彦、片山直之
  • Publisher: 科学評論者