Differentiation potential of Notch-1 positive human hematopoietic progenitors

• Project/Area Number: 20591154
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyushu University
• Principal Investigator: IWASAKI Hiromi Kyushu University, 大学病院, 講師 (20403925)
• Co-Investigator(Kenkyū-buntansha): AKASHI Koichi 九州大学, 医学研究院, 教授 (80380385)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 血液免疫学 / Notchシグナル / 樹状細胞 / 造血前駆細胞 / 単球

Research Abstract

We identified a novel human myeloid progenitor population that expressed Notch-1 at a high level. These Notch-1 positive progenitors preferentially differentiated into the monocyte/dendritic cell lineage in vitro. Notch-1 positive progenitors emerged in the culture of Notch-1 negative granulocyte/macrophage progenitors (GMPs), suggesting that they are more committed to the monocyte/dendritic cell lineage compared to GMPs. Indeed, they highly expressed monocyte/dendritic cell-affiliated genes including SpiB, FLT3, and PU.1. When Notch-1 positive progenitors were cultured in the presence of Notch-ligand (Delta-like 1), their progeny dendritic cells expressed lower levels of CD86 and HLA-DR compared to cells cultured without Delta-like 1, suggesting that Notch signals suppress the activation/maturation of dendritic cell lineage.

Research Products

• [Journal Article] 白血病幹細胞の成立機序と標的治療血液フロンティア (2010)
  • Author(s): 岩崎浩己、赤司浩一
  • Journal Title: 20(3) Pages: 149-158
• [Journal Article] High incidence of false-positive Aspergillus galactomannan test in multiple myeloma. (2010)
  • Author(s): Kikushige Y, Shima T, Takayanagi S, Urata S, Miyamoto T, Iwasaki H, Takenaka K, Teshima T, Tanaka T, Inagaki Y, Akashi K.
  • Journal Title: Cell Stem Cell Volume: 7 Pages: 708-17
  • Peer Reviewed
• [Journal Article] High incidence of HHV6-associated encephalitis/myelitis following a second unrelated cord blood transplantation. (2010)
  • Author(s): Mori Y, Miyamoto T, Nagafuji K, Kamezaki K, Yamamoto A, Saito N, Kato K, Takenaka K, Iwasaki H, Harada N, Abe Y, Teshima T, Akashi K.
  • Journal Title: Biol Blood Marrow Transplant Volume: 16 Pages: 1596-602
  • Peer Reviewed
• [Journal Article] High incidence of HHV6-associated encephalitis/myelitis following a second unrelated cord blood transplantation. (2010)
  • Author(s): Mori Y, Nagasaki Y, Kamezaki K, Takenaka K, Iwasaki H, Harada N, Miyamoto T, Abe Y, Shimono N, Akashi K, Teshima T.
  • Journal Title: Am J Hematol Volume: 85 Pages: 449-51
  • Peer Reviewed
• [Journal Article] Pulmonary nocardiosis developed in a hematopoietic stem cell transplant recipient with bronchiolitis obliterans. (2010)
  • Author(s): Nishida R, Mori Y, Iwasaki H, Tokuyama T, Kamezaki K, Nagasaki Y, Oka H, Miyawaki K, Saito N, Takenaka K, Harada N, Miyamoto T, Teshima T, Akashi K.
  • Journal Title: Intern Med Volume: 49 Pages: 1441-4
  • NAID: 130000299555
  • Peer Reviewed
• [Journal Article] Identification of the human eosinophil lineage-committed progenitor : Revision of phenotypic definition of the human common myeloid progenitor. (2009)
  • Author(s): Mori Y, Iwasaki H, Kohno K, Yoshimoto G, Kikushige Y, Okeda A, Uike N, Niiro H, Takenaka K, Nagafuji K, Miyamoto T, Harada M, Takatsu K, Akashi K
  • Journal Title: J Exp Med. 206 Pages: 183-93
  • Peer Reviewed
• [Journal Article] Origin of basophils and mast cells. (2009)
  • Author(s): 有信洋二郎, 岩崎浩己, 赤司浩一
  • Journal Title: Allergol Int. 58 Pages: 21-28
  • NAID: 10025108958
  • Peer Reviewed
• [Journal Article] 造血幹細胞から好酸球への分化機構血液・腫瘍科 (2009)
  • Author(s): 森康雄、岩崎浩己、赤司浩一
  • Journal Title: 58(2) Pages: 135-140
• [Journal Article] 好塩基球の発生・分化 (2009)
  • Author(s): 有信洋二郎、岩崎浩己、赤司浩一
  • Journal Title: アレルギー・免疫 6(3) Pages: 12-17
• [Journal Article] 白血病幹細胞の細胞生物学 (2009)
  • Author(s): 岩崎浩己、赤司浩一
  • Journal Title: 血液・腫瘍科 59(4) Pages: 467-475
  • NAID: 40019064280
• [Journal Article] Origin of basophils and mast cells (2009)
  • Author(s): Arinobu Y, et al.
  • Journal Title: Allergology International 58(1) Pages: 21-8
  • Peer Reviewed
• [Journal Article] 好塩基球の発生・分化 (2009)
  • Author(s): 有信洋二郎, 他
  • Journal Title: アレルギー・免疫 16(3) Pages: 12-7
• [Journal Article] 好酸球、好塩基球、肥満細胞の分化経路 (2009)
  • Author(s): 岩崎浩己, 他
  • Journal Title: 実験医学 27(20) Pages: 56-62
• [Journal Article] 白血病幹細胞の細胞生物学 (2009)
  • Author(s): 岩崎浩己, 他
  • Journal Title: 血液・腫瘍科 59(4) Pages: 467-75
• [Journal Article] Identification of the human eosinophil lineage-committed progenitor : Revision of phenotypic definition of the human common myeloid progenitor. (2009)
  • Author(s): Mori Y, et al.
  • Journal Title: The Journal of Experimental Medicine 206(1) Pages: 183-93
  • Peer Reviewed
• [Journal Article] Human flt3 is expressed at the hematopoietic stem cell and the granulocyte/macrophage progenitor stages to maintain cell survival. (2008)
  • Author(s): Kikushige Y, Yoshimoto G, Miyamoto T, Iino T, Mori Y, Iwasaki H, Niiro H, Takenaka K, Nagafuji K, Harada M, Ishikawa F, Akashi K
  • Journal Title: J Immunol. 180 Pages: 7358-7367
  • Peer Reviewed
• [Journal Article] Human flt3 is expressed at the hematopoietic stem cell and the granulocyte/macrophage progenitor stages to maintain cell survival. (2008)
  • Author(s): Kikushige Y, et al.
  • Journal Title: The Journal of Immunology 180(11) Pages: 7358-67
  • Peer Reviewed
• [Journal Article] Analysis of immune reconstitution after autologous CD34+ stem/progenit or cell transplantation for systemic sclerosis : predominant reconstitution of Th1 CD4+ T cells.
  • Author(s): Tsukamoto H, Nagafuji K, Horiuchi T, Mitoma H, Niiro H, Arinobu Y, Inoue Y, To K, Miyamoto T, Iwasaki H, Teshima T, Harada M, Akashi K.
  • Journal Title: Rheumatology (Oxford) Volume: (in press)
  • Peer Reviewed
• [Book] 血液フロンティア20(3) (2010)
  • Author(s): 岩崎浩己、赤司浩一
  • Publisher: 白血病幹細胞の成立機序と標的治療
• [Book] 好酸球、好塩基球、肥満細胞の分化経路実験医学 (2009)
  • Author(s): 岩崎浩己、赤司浩一
  • Publisher: アレルギー疾患の免疫機構
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