Identification of miRNA which rescues EBF1 deficiency indispensable for B cell lineage commitment
Project/Area Number |
17H04212
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Hematology
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Research Institution | Tokai University |
Principal Investigator |
KOTANI Ai 東海大学, 医学部, 教授 (00517477)
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Co-Investigator(Kenkyū-buntansha) |
穂積 勝人 東海大学, 医学部, 教授 (30246079)
伊川 友活 東京理科大学, 研究推進機構生命医科学研究所, 教授 (60450392)
大塚 正人 東海大学, 医学部, 教授 (90372945)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2017: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
|
Keywords | 細胞分化 / microRNA / 転写因子 / B細胞分化 / EBF1 / 細胞運命 / miRNA / 血液免疫学 |
Outline of Final Research Achievements |
Since miRNA overturns the classical concept that cell differentiation is determined by transcription factors, miR-195 was introduced into EBF1-deficient hematopoietic progenitor cells, which are essential for B cell differentiation, and we tried to induce differentiation. As a result, the B cell lineage cell surface marker CD19 could be reproducibly induced. In EBF1-deficient hematopoietic cells overexpressing miR-195, Atac-seq analysis revealed that the EBF1-binding genomic region was open. In miR-195-deficient mice, abnormal lymphocyte differentiation was observed, and the hypothesis was generally correct.
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Academic Significance and Societal Importance of the Research Achievements |
転写因子中心の細胞運命決定における従来の古典的概念を覆す、単一miRNAでの転写因子の補完が可能との研究成果の学術的意義は極めて高いと考える。事実、海外学会で高い評価が得られている。また、分化誘導療法はレチノイン酸を用いて、既に白血病治療で行われていることからも。本研究結果も同様の治療コンセプトで分化誘導療法に応用されるポテンシャルを有する。よって、既に癌治療において行われているmiRNAを用いた治療にもつながり、社会的意義も高いと考える。
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Report
(4 results)
Research Products
(27 results)
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[Journal Article] PD-L1 is induced on hepatocyte surface via CKLF-like MARVEL transmembrane domain-containing protein 6 upregulation by the anti-HBV drug Entecavir2020
Author(s)
1)Yamamoto Y, Kakisaki M,Kotaki R, Kurosaki N, Chiba T, Ando K,Shimizu T,Aoki T, Chamoto K,Kagawa T, *Kotani A
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Journal Title
International Immunology
Volume: in press
Related Report
Peer Reviewed
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[Journal Article] Dasatinib exacerbates splenomegaly of mice inoculated with Epstein-Barr virus-infected lymphoblastoid cell lines.2020
Author(s)
2)Kotaki R, Kawashima M, Yamamoto Y, Higuchi H, Nagashima E, Kurosaki N, Takamatsu M, Kikuti YY, Imadome KI, Nakamura N, *Kotani A.
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Journal Title
Sci Rep.
Volume: 10(1):
Issue: 1
Pages: 4355-4355
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] PD-L1/L2 protein levels rapidly increase on monocytes via trogocytosis from tumor cells in classical Hodgkin lymphoma2020
Author(s)
Kawashima M, Carreras J, Higuchi H, Kotaki R, Hoshina T, Okuyama K, Suzuki N, Kakizaki M, Miyatake Y, Ando K, Nakayama M, Umezu S, Horie R, Higuchi Y, Katagiri K, Goyama S, Kitamura T, Chamoto K, Yano S,Nakamura N, and A Kotani
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Journal Title
Leukemia
Volume: -
Issue: 9
Pages: 2405-2417
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] EBV LMP1 in Gingival Epithelium Potentially Contributes to Human Chronic Periodontitis via Inducible IL8 Production.2019
Author(s)
Watanabe N, Nodomi K, Koike R, Kato A, Takeichi O, Kotani AI, Kaneko T, Sakagami H, Takei M, Ogata Y, Sato S, Imai K.
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Journal Title
In Vivo.
Volume: 33(6)
Pages: 1793-1800
Related Report
Peer Reviewed
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[Journal Article] Role of exosomes as a proinflammatory mediator in the development of EBV-associated lymphoma.2018
Author(s)
Higuchi H, Yamakawa N, Imadome KI, Yahata T, Kotaki R, Ogata J, Kakizaki M, Fujita K, Lu J, Yokoyama K, Okuyama K, Sato A, Takamatsu M, Kurosaki N, Alba SM, Azhim A, Horie R, Watanabe T, Kitamura T, Ando K, Kashiwagi T, Matsui T, Okamoto A, Handa H, Kuroda M, Nakamura N, Kotani A.
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Journal Title
Blood
Volume: 131
Issue: 23
Pages: 2552-2567
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Imbalanced expression of polycistronic miRNA in acute myeloid leukemia.2017
Author(s)
Kotaki R, Higuchi H, Ogiya D, Katahira Y, Kurosaki N, Yukihira N, Ogata J, Yamamoto H, Mohamad Alba S, Azhim A, Kitajima T, Inoue S, Morishita K, Ono K, Koyama-Nasu R, Kotani A.
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Journal Title
Int J Hematol.
Volume: 106
Issue: 6
Pages: 811-819
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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