Roles of GATA1 and GATA2 in hematoietic stem cells

• Project/Area Number: 19591095
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: University of Tsukuba
• Principal Investigator: RITSUKO Shimizu University of Tsukuba, 大学院・人間総合科学研究科, 講師 (40226262)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2007: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 造血幹細胞移植学 / 血液腫瘍学 / 白血病 / 巨核球 / 転写因子 / GATA1 / ダウン症候群 / 一過性骨髄増殖性疾患 / GATA-1 / 白血病幹細胞 / Side population

Research Abstract

2種類のGata1遺伝子改変マウスを解析し、GATA1の量的異常と構造異常が、それぞれ赤血球、巨核球系列特異的前駆細胞の異常蓄積を引き起こすこと、しかし、GATA1の単独異常では白血病を発症せず、いずれの場合も白血病発症さらなる遺伝子の異常が引き金となることを明らかにした。また2種類のGata2遺伝子改変マウスの解析から、造血幹細胞や多能性前駆細胞の恒常性維持にはGATA2発現量のダイナミックな変化による精緻な制御が必須であることを明らかにした。

Research Products

• [Journal Article] Stem cells of GATAl-related leukemia undergo pernicious changes after 5-fluorouracil treatment (2009)
  • Author(s): Abe K, Shimizu R, Pan X, Hamada H, Yoshikawa H, Yamamoto M
  • Journal Title: Exp Heamtol 4 Pages: 435-445
  • Peer Reviewed
• [Journal Article] GATA-1 related leukemias (2008)
  • Author(s): Shimizu R. Engel JD and Yamamoto M.
  • Journal Title: Nat. Rev. Cancer 8 Pages: 279-287
  • NAID: 120003660458
  • Peer Reviewed
• [Journal Article] Impairment of erythroid, megakaryocytic differentiation by aleukemia-associated and t(9 ; 9)-derivedfusion gene product, SET/TAF-Ib-CAN/Nup214 (2008)
  • Author(s): Saito S, Nouno K, . Shimizu R, YamamotoM, Nagata K.
  • Journal Title: J Clin Pathol 214 Pages: 322-333
  • Peer Reviewed
• [Journal Article] Reduced BMP4 abundance in Gata2 hypomorphic mutant mice result in uropathies resembling human CAKUT (2008)
  • Author(s): Shimizu R, Hoshino T, Ohmori S, NaganoM, Pan X, Ohneda O, Khandekar M,Yamamoto M, Lim KC, Engel JD.
  • Journal Title: Gene Cells 13 Pages: 159-170
  • Peer Reviewed
• [Journal Article] GATA-1の機能異常と白血病-Leukemogenesis related to GATA-1 mutation- (2008)
  • Author(s): 安倍加奈子, 清水律子, 山本雅之
  • Journal Title: 日本産婦人科血液学会誌 17 Pages: 1-8
• [Journal Article] Saito S, Nouno K, Shimizu R, Yamamoto M, Nagata K. Impairment of erythroid and megakaryocytic differentiation by a leukemia-associated and t(9;9)-derived fusion gene product, SET/TAF-Ib-CAN/Nup214. (2008)
  • Author(s): Saito S, Nouno K, Shimizu R, Yamamoto M, Nagata K
  • Journal Title: J Clin Pathol 214 Pages: 322-333
  • Peer Reviewed
• [Journal Article] Reduced BMP4 abundance in Gata2 hypomorphic mutant mice result in uropathies resembling human CAKUT. (2008)
  • Author(s): Shimizu R. Hoshino T, Ohmori S, Nagano M, Pan X, Ohneda 0, Khandekar M, Yamamoto M, Lim KC, Engel JD
  • Journal Title: Gene Cells 13 Pages: 159-170
  • Peer Reviewed
• [Journal Article] GATA-1の機能異常と白血病-Leukemogenesis re1ated to GATA-1 mutation-. (2008)
  • Author(s): 安倍加奈子,清水律子,山本雅之
  • Journal Title: 日本産婦人科血液学会誌 17 Pages: 1-8
• [Journal Article] GATA-1 related leukemias. (2008)
  • Author(s): Shimizu R. Engel JD, Yamamoto M
  • Journal Title: Nat Rev Cancer 8 Pages: 279-287
  • NAID: 120003660458
  • Peer Reviewed
• [Journal Article] Impairment of erythroid and megakaryocytic differentiation by a leukemia-associated and t(9;9)-derived fusion gene product, SET/TAF-1β-CAN/Nup214 (2008)
  • Author(s): Saito S., et. al.
  • Journal Title: J Clin Pathol 214 Pages: 322-333
  • Peer Reviewed
• [Journal Article] Reduced BMP4 abundance in Gata2 hypomorphic mutant mice result in uropathies resembling human CAKUT (2008)
  • Author(s): Shimizu R., et. al.
  • Journal Title: Gene Cells 10 Pages: 159-170
  • Peer Reviewed
• [Journal Article] Characterization ofGATA-1^+ hemangioblastic cells in themouse embryo (2007)
  • Author(s): Yokomizo T, Takahashi S, Mochizuki N,Kuroha T, Ema M, Wakamatsu A, ShimizuR, Ohneda O, Osato M, Okada H, Komori T,Ogawa M, Nishikawa S, Ito Y,and Yamamoto, M.
  • Journal Title: EMBO J 26 Pages: 184-196
  • Peer Reviewed
• [Journal Article] Dynamic regulation of Gata factor levels ismore important than their identity (2007)
  • Author(s): Ferreira R, Wai A, Shimizu R, Gilemans N,Rottier R, von Lindern M, Ohneda K,Grosveld F, Yamamoto M, Philipsen S
  • Journal Title: Blood 109 Pages: 5481-5490
  • Peer Reviewed
• [Journal Article] A Gata2 intronic enhancer confers its pan-endothelia-specific regulation (2007)
  • Author(s): Khandekar M, Brandt W, Zhou Y, DagenaisS, Glover TW, Suzuki N, Shimizu R,Yamamoto M, Lim KC, Engel JD.
  • Journal Title: Development 134 Pages: 1703-1712
  • Peer Reviewed
• [Journal Article] GATA-1 self-association controls erythroid development in vivo (2007)
  • Author(s): Shimizu R, Trainor CD, Nishikawa K,Kobayashi M, Ohneda K, Yamamoto M.
  • Journal Title: J Biol Chem 282 Pages: 15862-15871
  • Peer Reviewed
• [Journal Article] In vivo promoter analysis on refeeding response of hepatic sterol regulatory element-binding protein-1c expression (2007)
  • Author(s): Takeuchi Y, Yahagi N, Nakagawa Y,Matsuzaka T, Shimizu R, Sekiya M, IizukaY, Ohashi K, Gotoda T, Yamamoto M,Nagai R, Kadowaki T, Yamada N, Osuga JI, Shimano H.
  • Journal Title: Biochem Biophys Res Commun 363 Pages: 329-335
  • NAID: 120007139072
  • Peer Reviewed
• [Journal Article] GATA因子スイッチングとGATA-1関連白血病 (2007)
  • Author(s): 清水律子, 山本雅之
  • Journal Title: 日本生化学学会誌 79 Pages: 941-952
  • NAID: 10019771823
  • Peer Reviewed
• [Journal Article] Characterization of GATA-1^+ hemangioblastic cells in the mouse embryo. (2007)
  • Author(s): Yokomizo T., et. al.
  • Journal Title: EMBO J 26 Pages: 184-196
  • Peer Reviewed
• [Journal Article] Dynamic regulation of Gata factor levels is more important than their identity. (2007)
  • Author(s): Ferreira R., et. al.
  • Journal Title: Blood 109 Pages: 5481-5490
  • Peer Reviewed
• [Journal Article] A Gata2 intronic enhancer confers its pan-endothelia-specific regulation. (2007)
  • Author(s): Khandekar M, et. al.
  • Journal Title: Development 134 Pages: 1703-1712
  • Peer Reviewed
• [Journal Article] GATA-1 self-association controls erythroid development in vivo. (2007)
  • Author(s): Shimizu R., et. al.
  • Journal Title: J Biol Chem 282 Pages: 15862-15871
  • Peer Reviewed
• [Journal Article] In vivo promoter analysis on refeeding response of hepatic sterol regulatory element-binding protein-1c expression (2007)
  • Author(s): Takeuchi Y., et. al.
  • Journal Title: Biochem Biophys Res Comm 363 Pages: 329-335
  • Peer Reviewed
• [Journal Article] GATA因子スイッチングとGATA-1関連白血病 (2007)
  • Author(s): 清水律子, 他
  • Journal Title: 日本生化学学会誌 79 Pages: 941-952
  • NAID: 10019771823
• [Journal Article] Stem cells ofGATA1-related leukemia undergopernicious changes after 5-fluorouraciltreatment
  • Author(s): Abe L. Shimizu R. Pan X, Hamada, H,Yoshikawa H, Yamamoto M.
  • Journal Title: Exp. Hematol
  • Peer Reviewed
• [Journal Article] GATA1-related leukemias
  • Author(s): Shimizu R., et. al.
  • Journal Title: Nat Rev Cancer (In press)
  • NAID: 120003660458
  • Peer Reviewed
• [Journal Article] GATA-1の機能異常と白血病
  • Author(s): 安部加奈子, 他
  • Journal Title: 日本産婦新生児血会誌 (In press)
• [Presentation] GATA1-FOG1相互作用の欠損は溶血性貧血を惹起する (2008)
  • Author(s): 長谷川敦史, 清水律子, 山本雅之
  • Organizer: 第2回リトリート大学院生研究発表会,東北大学萩ホール
  • Place of Presentation: 東北大学萩ホール,仙台
  • Year and Date: 2008-12-06
• [Presentation] 急性巨核芽球性白血病の多段階発がんに関与する遺伝子変異の同定 (2008)
  • Author(s): 小林枝里, 清水律子, 山本雅之
  • Organizer: 東北大学大学院医学系研究科医科学専攻ルネサンス事業第2回リトリート大学院生研究発表会
  • Place of Presentation: 東北大学萩ホール
  • Year and Date: 2008-12-06
• [Presentation] Gata1発現制御における血球特異的第1エキソンの機能 (2008)
  • Author(s): 小林枝里, 清水律子, 菊池優子, 山本雅之
  • Organizer: 東北大学グローバルCOENetwork Medicine創生拠点キックオフシンポジウム
  • Place of Presentation: 東北大学東北大学艮稜会館
  • Year and Date: 2008-09-01
• [Presentation] Functional Analysis of GATA-2 in Auditory and Neuronal System (2008)
  • Author(s): Hoshino T, Shimizu R, Yamamoto M, Hara A.
  • Organizer: Midwinter Research Meeting of Association for Research inOtolaryngology
  • Place of Presentation: Phoenix, Arizona, USA
• [Presentation] Induction of Hyperproliferative Fetal Megakaryopoiesis by an N-terminally Truncated GATA1 Mutant (2008)
  • Author(s): Shimizu R, Engel JD, Yamamoto M.
  • Organizer: The 50th ASH Annual Meeting, Moscone Convention Center
  • Place of Presentation: San Francisco, CA
• [Presentation] Gata1 Gene Regulation and GATA1-related Leukemia (2008)
  • Author(s): Yamamoto M, Moriguchi, T, Suzuki, M, Shimizu R.
  • Organizer: The 16th Conference on Hemoglobin Switching
  • Place of Presentation: Asilomar, California
• [Presentation] Induction of Hyperproliferative Fetal Megakaryopoiesis by an N-terminally Truncated GATA1 Mutant (2008)
  • Author(s): Shimizu R, Engel JD, Yamamoto M.
  • Organizer: The 16th Conference on Hemoglobin Switching
  • Place of Presentation: Asilomar,California
• [Presentation] Gata1発現制御における血球特異的第1エキソンの機能 (2008)
  • Author(s): 小林枝里, 清水律子, 菊池優子, 山本雅之
  • Organizer: 遺伝情報DECODE-平成20年度合同班会議
  • Place of Presentation: 静岡県熱海ホテルニューアカオ
• [Presentation] 造血幹細胞の未分化性維持機構に関わる骨髄ニッチの役割 (2008)
  • Author(s): 清水律子
  • Organizer: 特定領域研究<細胞の運命と挙動を支配する細胞外環境のダイナミズム>京都国際会館
  • Place of Presentation: 京都国際会館,京都
• [Presentation] GATA1-FOG1相互作用の欠損は溶血性貧血を惹起する (2008)
  • Author(s): 長谷川敦史, 清水律子, 山本雅之
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会(BMB2008)神戸ポートアイランド
  • Place of Presentation: 神戸
• [Presentation] Induction of hyperproliferative fetal megakaryopoiesis by an N-terminally truncated GATA1 mutant. (2008)
  • Author(s): Shimizu R
  • Organizer: The 16th Conference on. Hemoglobin Switching
  • Place of Presentation: Asilomar, CA, USA
• [Presentation] Induction of hyperproliferative fetal megakaryopoiesis by an N-terminally truncated GATA1 mutant. (2008)
  • Author(s): Shimizu R
  • Organizer: The 50th ASH Annual Meeting
  • Place of Presentation: San Francisco, CA, USA
• [Presentation] Transcription Factor GATA-2 Regulates Self-renewal of Hematopoietic Stem Cells (2007)
  • Author(s): Shimizu R, Hoshino T, Suzuki N, Yamamoto M.
  • Organizer: Stem cell Gordon Conference
  • Place of Presentation: Big Sky, Montana, USA
• [Presentation] Stem cells in GATA-1 knockdown leukemia are heldin quiescence, released into cell cycle after5-fluorouracil treatment (2007)
  • Author(s): Shimizu R, Abe K, Yamamoto M.
  • Organizer: The 11^<th> Germany-Japan Cancer Workshop, Kyoto
  • Place of Presentation: Japan
• [Presentation] Analyses ofleukemic stem cells of GATA-1 related leukemia (2007)
  • Author(s): Abe K, Shimizu R, Pan X, Hamada H, Yoshikawa H, Yamamoto M.
  • Organizer: Stem cell Gordon Conference
  • Place of Presentation: Big Sky, Montana, USA
• [Presentation] Increase of hematopoietic progenitors but impairment of erythroid, megakaryocytic differentiation in transgenic mice expressing SET-CAN (2007)
  • Author(s): Saito S, Nouno K, Shimizu R, Yamamoto M, Nagata K.
  • Organizer: Stem cell Gordon Conference
  • Place of Presentation: Big Sky, Montana, USA
• [Presentation] Leukemia-related transcription factor TEL expands erythroid precursors (2007)
  • Author(s): Eguchi-Ishimae M, Eguchi M, Maki K, Shimizu R, Yamamoto M, Mitani K.
  • Organizer: Annual meeting of American Society of Hematology, Georgia World congress Center
  • Place of Presentation: Atlanta, GA, USA
• [Presentation] Analyses of leukemic stem cells of GATA-1 related leukemia (2007)
  • Author(s): 安部加奈子, 清水律子, 吉川裕之, 山本雅之
  • Organizer: パシフィコ横浜
  • Place of Presentation: 横浜
• [Presentation] 白血病関連転写因子TELは赤芽球系前駆細胞を増加させる (2007)
  • Author(s): 江口真理子, 石前峰斎, 牧和宏, 清水律子, 山本雅之, 三谷絹子
  • Organizer: 第69回日本血液学会
  • Place of Presentation: パシフィコ横浜,横浜
• [Presentation] GATA-1機能異常による白血病発症メカニズムの解析 (2007)
  • Author(s): 清水律子, 山本雅之
  • Organizer: 厚生労働省癌研究助成金「造血器腫瘍における染色体転座関連遺伝子の基礎的・臨床的研究」班会議
  • Place of Presentation: 国立がんセンター
• [Presentation] 白血病関連転写因子TELは赤血球系前駆細胞を増加させる (2007)
  • Author(s): 江口真理子, 石前峰斎, 牧和宏, 清水律子, 山本雅之, 三谷絹子
  • Organizer: 第69回日本血液学会・第49回日本臨床血液学会
  • Place of Presentation: 合同大会パシフィコ横浜,横浜
• [Presentation] 赤血球造血におけるSUMO 化GATA-1 の生理的意義(Functional Roles of GATA-1Sumoylation in Erythropoiesis) (2007)
  • Author(s): 清水律子, 大森慎也, 森口尚, 山本雅之
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学学会大会
  • Place of Presentation: 合同大会パシフィコ横浜,横浜
• [Presentation] 聴器・神経系におけるGATA-2の機能解析(Functionalanalysis of GATA-1 in auditory and neuronalsystem) (2007)
  • Author(s): 星野朝文, 清水律子, 深水昭吉, 田渕経司, 原晃, 山本雅之
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学学会大会
  • Place of Presentation: 合同大会パシフィコ横浜,横浜
• [Presentation] GATA-1機能異常による白血病の発症を修飾する因子の遺伝学的解析(Genetic analysis of modifying factors orleukemogenesis caused by GATA-1dysfunction) (2007)
  • Author(s): 安部加奈子, 清水律子, 濱田洋実, 吉川裕之, 山本雅之
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学学会大会
  • Place of Presentation: 合同大会パシフィコ横浜,横浜
• [Presentation] GATA-1タンパク質発現における血球特異的第1エキソンの機能(Multiplefunctions of the Gata1 gene first exon in hematopoiesis) (2007)
  • Author(s): 小林枝里, 清水律子, 菊池優子, 山本雅之
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学学会大会
  • Place of Presentation: 合同大会パシフィコ横浜,横浜
• [Presentation] Refeeding によるSREBP-1c遺伝子の転写活性調節機構の解析(Analysis of SREBP-c gene promoteractivity by refeeding) (2007)
  • Author(s): 竹内謙憲, 矢作直也, 中川嘉, 関谷元博,松坂賢, 位高啓史, 片岡一則, 長井良三,清水律子, 山本雅之, 山田信博, 大須賀淳一, 門脇孝 島野仁
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学学会大会
  • Place of Presentation: 合同大会パシフィコ横浜、横浜
• [Presentation] Sumo-modification of GATA-1 at lysine-137 is important for erythropoiesis through its ability to repress Gata2 transcription (2007)
  • Author(s): Shimizu R., et. al.
  • Organizer: The 4th International Symposium on GATA Factors
  • Place of Presentation: Capli, ltaly
• [Presentation] Analyses of leukemic stem cells of GATA-1 related leukemia (2007)
  • Author(s): Abe K., et. al.
  • Organizer: Stem cell Gordon Conference
  • Place of Presentation: Big Sky, Montana, USA
• [Presentation] Stem cells in GATA-1 knockdown leukemia are held in quiescence and released into cell cycle after 5-fluorouracil treatment (2007)
  • Author(s): Shimizu R., et. al.
  • Organizer: The 11th Germany-Japan Cancer Workshop
  • Place of Presentation: Kyoto, Japan
• [Remarks] がん特定統合がん領域国際交流委員会海外派遣事業報告書(第50回アメリカ血液学会)「第50回アメリカ血液学会総会に参加して」、2008年12月
  • URL: http://gantoku3.umin.jp/topics/shimizu.html