The functional analysis of GATA2 in mature mast cells

• Project/Area Number: 25860221
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Takasaki University of Health and Welfare
• Principal Investigator: OHMORI Shin'ya 高崎健康福祉大学, 薬学部, 助手 (10509194)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 転写因子 / Gata2 / Cebpa / 細胞分化 / マスト細胞 / 脱分化 / 分化転換 / 生体分子医学 / GATA2 / BMMC / 形質転換

Outline of Final Research Achievements

To clarify roles GATA2 plays in the BMMCs, the DNA binding C-finger domain of GATA2 was genetically disrupted by Cre-LoxP system in BMMCs (G2ΔCF-BMMCs). We found that deletion of GATA2 CF results in a loss of mast cell identity of BMMCs, whereas the expression of Mac1- and/or Ly-6C/G-positive cells was significantly increased in G2ΔCF-BMMCs. Furthermore, GATA2 ablation led to a significant upregulation of C/EBPα, a key player of myeloid cell differentiation, and forced expression of C/EBPα in wild-type BMMCs phenocopied the GATA2ΔCF cells. Our findings suggest that the repression of Cebpa by GATA2 is essential for maintaining mast cell identity in BMMCs.

Research Products

• [Journal Article] GATA2 is critical for the maintenance of cellular identity in differentiated mast cells derived from mouse bone marrow. (2015)
  • Author(s): Ohmori S, Moriguchi T, Noguchi Y, Ikeda M, Kobayashi K, Tomaru N, Ishijima Y, Ohneda O, Yamamoto M, Ohneda K.
  • Journal Title: Blood Volume: 125 Issue: 21 Pages: 3306-3315
  • DOI: 10.1182/blood-2014-11-612465
  • Peer Reviewed / Open Access
• [Journal Article] Transcription factor GATA1 is dispensable for mast cell differentiation in adult mice. (2014)
  • Author(s): Ohneda K, Moriguchi T, Ohmori S, Ishijima Y, Satoh H, Philipsen S, Yamamoto M.
  • Journal Title: Mol Cell Biol. Volume: 34 Issue: 10 Pages: 1812-1826
  • DOI: 10.1128/mcb.01524-13
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] GATA factor switching from GATA2 to GATA1 contributes to erythroid differentiation (2013)
  • Author(s): Suzuki M, Kobayashi-Osaki M, Tsutsumi S, Pan X, Ohmori S, Takai J, Moriguchi T, Ohneda O, Ohneda K, Shimizu R, Kanki Y, Kodama T, Aburatani H, Yamamoto M
  • Journal Title: Genes Cells Volume: 18 Issue: 11 Pages: 921-933
  • DOI: 10.1111/gtc.12086
  • Peer Reviewed
• [Journal Article] Establishment of erythroleukemic GAK14 cells and characterization of GATA1 N-terminal domain (2013)
  • Author(s): Mukai HY, Suzuki M, Nagano M, Ohmori S, Otsuki A, Tsuchida K, Moriguchi T, Ohneda K, Shimizu R, Ohneda O, Yamamoto M,
  • Journal Title: Genes Cells Volume: 18 Issue: 10 Pages: 886-898
  • DOI: 10.1111/gtc.12084
  • Peer Reviewed
• [Journal Article] Mast cell deficiency results in the accumulation of preadipocytes in adipose tissue in both obese and non-obese mice. (2013)
  • Author(s): Ishijima Y, Ohmori S, Ohneda K.
  • Journal Title: FEBS Open Bio. Volume: 4 Pages: 18-24
  • Peer Reviewed
• [Presentation] GATA2がCebpaの転写を抑制することが骨髄マスト細胞の分化形質維持に必要である (2014)
  • Author(s): 大森 慎也, 登丸 菜月, 石嶋 康史, 森口 尚, 山本 雅之, 大根田 絹子
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] マスト細胞におけるGATA2によるCebpa遺伝子の発現抑制機構の解析 (2014)
  • Author(s): 小林浩太, 大森 慎也, 石嶋 康史, 森口 尚, 山本 雅之, 大根田 絹子
  • Organizer: 平成26年度日本生化学会関東支部例会
  • Place of Presentation: 水戸
  • Year and Date: 2014-06-14
• [Presentation] GATA2欠失マスト細胞の分化転換能の解析 (2014)
  • Author(s): 野口由紀, 大森 慎也, 石嶋 康史, 森口 尚, 山本 雅之, 大根田 絹子
  • Organizer: 平成26年度日本生化学会関東支部例会
  • Place of Presentation: 水戸
  • Year and Date: 2014-06-14
• [Presentation] GATA2はマスト細胞の分化形質の維持に必須である。 (2013)
  • Author(s): 大森慎也、石嶋康史、森口尚、山本雅之、大根田絹子
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
• [Presentation] GATA2によるcebpa遺伝子の発現抑制が骨髄マスト細胞の分化形質の維持に必須である。 (2013)
  • Author(s): 大森慎也、石嶋康史、野口由紀、森口尚、山本雅之、大根田絹子
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] マスト細胞の欠失により脂肪組織に脂肪前駆細胞が蓄積する。 (2013)
  • Author(s): 石嶋康史、大森慎也、大根田絹子
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Remarks] 高崎健康福祉大学 薬学部 分子生体制御学研究室
  • URL: http://www.takasaki-u.ac.jp/p_yaku_labo/yaku-02-01/