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Comprehensive analysis of gene expression regulation during mononuclear phagocyte development

Research Project

Project/Area Number 15H04860
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionYokohama City University

Principal Investigator

Tamura Tomohiko  横浜市立大学, 医学研究科, 教授 (50285144)

Co-Investigator(Kenkyū-buntansha) 中林 潤  横浜市立大学, 先端医科学研究センター, 准教授 (80322733)
Co-Investigator(Renkei-kenkyūsha) KUROTAKI Daisuke  横浜市立大学, 医学部, 講師 (10568455)
NISHIYAMA Akira  横浜市立大学, 医学部, 准教授 (80589664)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Keywordsエンハンサー / 単球 / 樹状細胞 / 転写因子 / ChIP-seq / 血球細胞分化 / 遺伝子発現制御 / 細胞分化 / 発生・分化 / 遺伝子 / 発現制御 / 単核貪食細胞分化
Outline of Final Research Achievements

Monocytes and dendritic cells (DCs), called mononuclear phagocytes, are critical for host defense and tissue homeostasis. These cells develop from bone marrow hematopoietic stem cells via intermediate progenitors. However, molecular mechanisms underlying the regulation of gene expression during monocyte and DC development still remain obscure. In this research project, we analyzed the genome-wide dynamics of enhancer landscape, gene expression, and chromatin binding of key transcription factors in various differentiation stages of myeloid cells. We found that the chromatin binding of IRF8, which recruits binding of PU.1, induces the formation of monocyte and DC-specific enhancers in the progenitor stages, leading to the future expression of genes that confer the characteristics of mononuclear phagocytes. These results contribute to a comprehensive understanding of how transcription factors affect chromatin to regulate gene expression during cell differentiation.

Report

(3 results)
  • 2017 Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (42 results)

All 2017 2016 2015 Other

All Int'l Joint Research (2 results) Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (30 results) (of which Int'l Joint Research: 8 results,  Invited: 8 results) Remarks (1 results)

  • [Int'l Joint Research] NIAID, NIH/NICHD, NIH(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] NICHD, NIH/NIAID, NIH(米国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 転写因子によるミエロイド系細胞の分化制御2016

    • Author(s)
      田村 智彦, 西山 晃
    • Journal Title

      日本臨床

      Volume: 74 Pages: 481-486

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Lyn Kinase Suppresses the Transcriptional Activity of IRF5 in the TLR-MyD88 Pathway to Restrain the Development of Autoimmunity.2016

    • Author(s)
      Ban T., Sato G.R., Nishiyama A., Akiyama A., Takasuna M., Umehara M., Suzuki S., Ichino M., Matsunaga S., Kimura A., Kimura Y., Yanai H., Miyashita S., Kuromitsu J., Tsukahara K., Yoshimatsu K., Endo I., Yamamoto T., Hirano H., Ryo A., Taniguchi T., Tamura T.
    • Journal Title

      Immunity

      Volume: 45 Issue: 2 Pages: 319-332

    • DOI

      10.1016/j.immuni.2016.07.015

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Transcriptional and epigenetic regulation of innate immune cell development by the transcription factor, interferon regulatory factor-82016

    • Author(s)
      Kurotaki D., Tamura T.
    • Journal Title

      Journal of Interferon & Cytokine Research

      Volume: 36 Issue: 7 Pages: 433-441

    • DOI

      10.1089/jir.2015.0138

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of basophil and mast cell development by transcription factors2016

    • Author(s)
      Sasaki H, Kurotaki D, Tamura T
    • Journal Title

      Allergology International

      Volume: 65 Issue: 2 Pages: 127-134

    • DOI

      10.1016/j.alit.2016.01.006

    • NAID

      130005290401

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Guest editorial: Transcriptional control in myeloid cell development and related diseases2015

    • Author(s)
      Tamura T.
    • Journal Title

      International Journal of Hematology

      Volume: 101 Issue: 4 Pages: 317-318

    • DOI

      10.1007/s12185-015-1770-8

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of myelopoiesis by the transcription factor IRF82015

    • Author(s)
      Tamura T, Kurotaki D, Koizumi S.
    • Journal Title

      International Journal of Hematology

      Volume: 101 Issue: 4 Pages: 342-351

    • DOI

      10.1007/s12185-015-1761-9

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcription factor IRF1 is responsible for IRF8-mediated IL-1β expression in reactive microglia.2015

    • Author(s)
      Masuda T, Iwamoto S, Mikuriya S, Tozaki-Saitoh H, Tamura T, Tsuda M, Inoue K
    • Journal Title

      J Pharmacol Sci

      Volume: 128(4) Issue: 4 Pages: 216-220

    • DOI

      10.1016/j.jphs.2015.08.002

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 転写因子IRF8による好塩基球とマスト細胞の分化制御2015

    • Author(s)
      佐々木悠, 黒滝大翼, 田村智彦
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 63 Pages: 593-596

    • NAID

      40020505142

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Transcription factors in the development of myeloid cells2015

    • Author(s)
      田村 智彦, 小泉 真一, 黒滝 大翼
    • Journal Title

      Rinsho Ketsueki

      Volume: 56 Issue: 10 Pages: 1861-1870

    • DOI

      10.11406/rinketsu.56.1861

    • NAID

      130005103301

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Presentation] Single cell RNA-seq reveals the earliest dendritic cell-primed hematopoietic progenitors2017

    • Author(s)
      Kurotaki D, Kawase W, Nakabayashi J, Morse HC, Ozato K, Suzuki Y, Tamura T
    • Organizer
      新学術領域「先進ゲノム支援」国際シンポジウム「The Start of New Genomics」
    • Place of Presentation
      東京大学伊藤謝恩ホール(東京都文京区)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 樹状細胞へ運命決定された早期前駆細胞の発見2017

    • Author(s)
      川瀬 航, 黒滝 大翼, 中林 潤, Herbert C. Morse III, Keiko Ozato, 鈴木 穣, 田村 智彦
    • Organizer
      冬の若手ワークショップ2017
    • Place of Presentation
      一宮シーサイドオーツカ(千葉県一宮町)
    • Related Report
      2016 Annual Research Report
  • [Presentation] IRF Transcription Factors in the Development and Function of Mononuclear Phagocytes2017

    • Author(s)
      Tamura T
    • Organizer
      The 2017 Japan-NIH Joint Symposium
    • Place of Presentation
      東北大学星陵オーディトリアム(宮城県仙台市)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Isolation and characterization of the earliest dendritic cell-primed progenitors2017

    • Author(s)
      Kurotaki D, Kawase W, Nakabayashi J, Morse HC, Ozato K, Suzuki Y, Tamura T
    • Organizer
      The 2017 Japan-NIH Joint Symposium
    • Place of Presentation
      東北大学星陵オーディトリアム(宮城県仙台市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 単一細胞RNA-seqによる早期樹状細胞前駆細胞の同定2017

    • Author(s)
      黒滝 大翼, 中林 潤, Herbert C. Morse III, Keiko Ozato, 鈴木 穣, 田村 智彦
    • Organizer
      第21回造血器腫瘍研究会
    • Place of Presentation
      熊本大学山崎記念館(熊本県熊本市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 単球・樹状細胞分化におけるエンハンサー動態の解析と転写因子IRF8の役割2016

    • Author(s)
      黒滝大翼, 中林 潤, 西山 晃, 佐々木悠, 金子尚史,小泉真一, Keiko Ozato, 鈴木 穣, 田村智彦
    • Organizer
      第20回造血器腫瘍研究会
    • Place of Presentation
      かずさアーク(千葉県木更津市)
    • Year and Date
      2016-02-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] 単球及び樹状細胞の前駆細胞における遺伝子発現とエンハンサー形成の階層的制御2016

    • Author(s)
      黒滝大翼, 中林 潤, 西山 晃, 佐々木悠, 金子尚史,小泉真一, Keiko Ozato, 鈴木 穣, 田村智彦
    • Organizer
      冬の若手ワークショップ2016
    • Place of Presentation
      山中湖畔荘ホテル清渓(山梨県山中湖村)
    • Year and Date
      2016-02-04
    • Related Report
      2015 Annual Research Report
  • [Presentation] 単球分化でのKlf4 遺伝子発現にて見いだされた、遠位エンハンサーと遺伝子間の多段階、かつ双方向性の活性化機構の解析2016

    • Author(s)
      西山 晃、中林 潤、黒滝大翼、田村智彦
    • Organizer
      冬の若手ワークショップ2016
    • Place of Presentation
      山中湖畔荘ホテル清渓(山梨県山中湖村)
    • Year and Date
      2016-02-04
    • Related Report
      2015 Annual Research Report
  • [Presentation] A genome-wide analysis of chromosomal interactions involving the IRF8-dependent Klf4 enhancer in monocyte differentiation2016

    • Author(s)
      Nishiyama A, Nakabayashi J, Tamura T
    • Organizer
      第33回染色体ワークショップ、第14回核ダイナミクス研究会
    • Place of Presentation
      松島一の坊(宮城県宮城郡松島町)
    • Year and Date
      2016-01-13
    • Related Report
      2015 Annual Research Report
  • [Presentation] Epigenetic regulation of monocyte and dendritic cell development by the transcription factor IRF82016

    • Author(s)
      Tamura T
    • Organizer
      The 24th International Symposium on Molecular Cell Biology of Macrophages
    • Place of Presentation
      御茶ノ水ソラシティカンファレンスセンター(東京都千代田区)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 転写因子IRF8によるミエロイド系細胞分化のエピジェネティック制御2016

    • Author(s)
      黒滝 大翼
    • Organizer
      第22回血液科学セミナー
    • Place of Presentation
      ヤクルトホール(東京都港区)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Hierarchical regulation of enhancer establishment and gene expression by transcription factors during mononuclear phagocyte development2016

    • Author(s)
      Kurotaki D, Nakabayashi J, Nishiyama A, Sasaki H, Kaneko N, Ozato K, Suzuki Y, Tamura T
    • Organizer
      International Congress of Immunology 2016
    • Place of Presentation
      Melbourne Convention and Exhibition Centre, Melbourne, Australia
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The transcription factor IRF8 and enhancer landscape dynamics in the development of mononuclear phagocytes2016

    • Author(s)
      Tamura T
    • Organizer
      第78回日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 単一細胞RNA-seqによる早期樹状細胞前駆細胞の同定2016

    • Author(s)
      黒滝 大翼, 中林 潤, Herbert C. Morse III, Keiko Ozato, 鈴木 穣, 田村 智彦
    • Organizer
      第78回日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 単核貪食細胞分化におけるエンハンサーランドスケープ動態と転写因子IRF82016

    • Author(s)
      田村 智彦
    • Organizer
      第41回神戸ラボ全体研究会議
    • Place of Presentation
      神戸バイオテクノロジー研究・人材育成センター(兵庫県神戸市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Transcription factor IRF8 governs enhancer landscape dynamics in the development of mononuclear phagocytes.2016

    • Author(s)
      Tamura T
    • Organizer
      The International Conference on Transcription Cycle 2016
    • Place of Presentation
      東京大学小柴ホール(東京都文京区)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Single-cell RNA-seq reveals a novel dendritic cell-primed early progenitor population2016

    • Author(s)
      Kurotaki D, Kawase W, Nakabayashi J, Morse HC, Ozato K, Tamura T
    • Organizer
      第45回日本免疫学会学術集会
    • Place of Presentation
      沖縄コンベンションセンター(沖縄県宜野湾市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Enhancer Landscape Dynamics and the Role of IRF8 in Mononuclear Phagocyte Development2015

    • Author(s)
      Kurotaki D, Nakabayashi J, Nishiyama A, Sasaki H, Kaneko N, Koizumi S, Ozato K, Suzuki Y, Tamura T
    • Organizer
      57th American Society of Hematology Annual Meeting and Exposition
    • Place of Presentation
      Orange County Convention Center, Orlando, FL, USA
    • Year and Date
      2015-12-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 単球分化を促す転写因子IRF8により活性化されるKlf4遠位エンハンサーを起点とした染色体間クロマチンネットワークの解析2015

    • Author(s)
      西山 晃, 中林 潤, 岡部篤史, 堤 修一, 油谷浩幸, 田村智彦
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸ポートピアアイランド(兵庫県神戸市)
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] Transcription factor IRF8 governs the enhancer landscape dynamics during monocyte and dendritic cell development2015

    • Author(s)
      Kurotaki D, Nakabayashi J, Nishiyama A, Sasaki H, Kaneko N, Koizumi S, Ozato K, Suzuki Y, Tamura T
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸ポートピアアイランド(兵庫県神戸市)
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Transcription factor IRF8 governs the enhancer landscape dynamics in mononuclear phagocyte development2015

    • Author(s)
      Kurotaki D, Nakabayashi J, Nishiyama A, Sasaki H, Kaneko N, Koizumi S, Ozato K, Tamura T
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] ミエロイド系細胞の分化と転写因子2015

    • Author(s)
      田村智彦
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      ホテル金沢(石川県金沢市)
    • Year and Date
      2015-10-18
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 転写因子IRF8によるマスト細胞の分化制御2015

    • Author(s)
      佐々木悠, 黒滝大翼, 田村智彦
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      ホテル金沢(石川県金沢市)
    • Year and Date
      2015-10-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] 単球-樹状細胞系譜分化におけるエンハンサーランドスケープの解読2015

    • Author(s)
      黒滝大翼, 中林 潤, 西山 晃, 佐々木悠, 金子尚史, 小泉真一, Keiko Ozato, 鈴木 穣, 田村智彦
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      ホテル金沢(石川県金沢市)
    • Year and Date
      2015-10-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] BCR-ABLは樹状細胞前駆細胞におけるPU.1結合や活性化エンハンサーの分布を変化させる2015

    • Author(s)
      小泉真一, 西山 晃, 中林 潤, 佐々木悠, 宮下和甫, 黒滝大翼, 田村智彦
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      ANAクラウンプラザホテル金沢(石川県金沢市)
    • Year and Date
      2015-10-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] A role of the transcription factor IRF8 in basophil and mast cell development2015

    • Author(s)
      Sasaki H, Kurotaki D, Osato N, Sato H, Sasaki I, Koizumi S, Wang H, Kaneda C, Nishiyama A, Kaisho T, Aburatani H, Morse HC III, Ozato K, Tamura T
    • Organizer
      International Society for Experimental Hematology 44th Annual Scientific Meeting
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2015-09-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] IRF8 inhibits the activity of C/EBPα to restrain mononuclear phagocyte progenitors from differentiating into neutrophils2015

    • Author(s)
      Kurotaki D, Yamamoto M, Nishiyama A, Uno K, Ban T, Ichino M, Sasaki H, Matsunaga S, Yoshinari M, Ryo A, Nakazawa M, Ozato K, Tamura T
    • Organizer
      International Society for Experimental Hematology 44th Annual Scientific Meeting
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Enhancer landscape dynamics during monocyte and dendritic cell development and the role of the transcription factor IRF82015

    • Author(s)
      Kurotaki D, Nakabayashi J, Nishiyama A, Sasaki H, Kaneko N, Koizumi S, Ozato K, Suzuki Y, Tamura T
    • Organizer
      International Society for Experimental Hematology 44th Annual Scientific Meeting
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 好塩基球、マスト細胞分化における転写因子IRF8の役割2015

    • Author(s)
      佐々木悠, 黒滝大翼, 大里直樹, 佐藤英明, 佐々木泉, 小泉真一, Hongsheng Wang, 金田智香, 西山 晃, 改正恒康, 油谷浩幸, Herbert C. Morse III, Keiko Ozato, 田村智彦
    • Organizer
      第11回麒麟塾
    • Place of Presentation
      コクヨホール(東京都港区)
    • Year and Date
      2015-07-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] 転写因子IRF8による好塩基球分化制御機構の解明2015

    • Author(s)
      黒滝大翼, 佐々木悠, 大里直樹, 佐藤英明, 佐々木泉, 小泉真一, Hongsheng Wang, 金田智香, 西山 晃, 改正恒康, 油谷浩幸, Herbert C. Morse III, Keiko Ozato, 田村智彦
    • Organizer
      第26回生体防御学会学術総会
    • Place of Presentation
      生涯学習センター(東京都台東区)
    • Year and Date
      2015-07-10
    • Related Report
      2015 Annual Research Report
  • [Remarks] 横浜市立大学医学部免疫学教室ホームページ

    • URL

      http://www-user.yokohama-cu.ac.jp/~immunol/

    • Related Report
      2016 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2023-12-25  

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