Establishment of in vivo model of anemia by shRNA transgene controlled by erythroid-lineage specific promoter

• Project/Area Number: 15K09447
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Tohoku University
• Principal Investigator: FUJIWARA TOHRU 東北大学, 大学病院, 講師 (60333796)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 血液内科学 / 貧血 / 赤血球分化 / 転写因子

Outline of Final Research Achievements

To establish in vivo model of anemia, we established and crossed 1) GATA-1 promoter (G1HRD)/reverse tetracycline transactivator (rtTA)-transgenic mice and 2) Tetracycline-responsive element (TRE)/Lmo2 shRNA-tranegenic mice. In the established mice (Tg-TRE-Lmo2 shRNA::Tg-G1HRD-rtTA), Lmo2 shRNA is expected to be induced specifically in erythroblasts by tetracycline administration, leading to the onset of anemia. Our established system would be applied to establish wide variety of in vivo anemia models by targeting to erythroid genes other than Lmo2.

Research Products

• [Journal Article] A defined culture method enabling the establishment of ring sideroblasts from induced pluripotent cells of X-linked sideroblastic anemia. (2018)
  • Author(s): 1.Hatta S, Fujiwara T, Yamamoto T, Saito K, Kamata M, Tamai Y, Kawamata S, Harigae H.
  • Journal Title: Haematologica. Volume: - Issue: 5 Pages: 188-191
  • DOI: 10.3324/haematol.2017.179770
  • Peer Reviewed / Open Access
• [Journal Article] Establishment of a Screening System to Identify Novel GATA-2 Transcriptional Regulators (2018)
  • Author(s): Ohashi K, Fujiwara T, Onodera K, Saito Y, Ichikawa S, Kobayashi M, Okitsu Y, Fukuhara N, Onishi Y, Harigae H.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 244 Issue: 1 Pages: 41-52
  • DOI: 10.1620/tjem.244.41
  • NAID: 130006315364
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed / Open Access
• [Journal Article] Dynamics of absorption, metabolism, and excretion of 5-aminolevulinic acid in human intestinal Caco-2 cells. (2017)
  • Author(s): Saito K, Fujiwara T, Ota U, Hatta S, Ichikawa S, Kobayashi M, Okitsu Y, Fukuhara N, Onishi Y, Ishizuka M, Tanaka T, Harigae H
  • Journal Title: Biochemistry and Biophysics Reports Volume: 11 Pages: 105-111
  • DOI: 10.1016/j.bbrep.2017.07.006
  • Peer Reviewed / Open Access
• [Journal Article] Effects of in vivo deletion of GATA2 in bone marrow stromal cells (2017)
  • Author(s): Hasegawa S, Fujiwara T, Okitsu Y, Kato H, Sato Y, Fukuhara N, Onishi Y, Shimizu R, Yamamoto M, Harigae H.
  • Journal Title: Experimental Hematology Volume: 56 Pages: 31-45
  • DOI: 10.1016/j.exphem.2017.08.004
  • Peer Reviewed / Open Access
• [Journal Article] A novel heterozygous ALAS2 mutation in a female with macrocytic sideroblastic anemia resembling myelodysplastic syndrome with ring sideroblasts: a case report and literature review (2017)
  • Author(s): Fujiwara T, Fukuhara N, Ichikawa S, Kobayashi M, Okitsu Y, Onishi Y, Furuyama K, Harigae H
  • Journal Title: Annals of Hematology Volume: 96(11) Issue: 11 Pages: 1955-1957
  • DOI: 10.1007/s00277-017-3106-7
  • Peer Reviewed / Open Access
• [Journal Article] Forced FOG1 expression in erythroleukemia cells: Induction of erythroid genes and repression of myelo-lymphoid transcription factor PU.1. (2017)
  • Author(s): Fujiwara T, Sasaki K, Saito K, Hatta S, Ichikawa S, Kobayashi M, Okitsu Y, Fukuhara N, Onishi Y, Harigae H.
  • Journal Title: Biochem Biophys Res Commun Volume: 485 Issue: 2 Pages: 380-387
  • DOI: 10.1016/j.bbrc.2017.02.068
  • Peer Reviewed
• [Journal Article] GATA Transcription Factors: Basic Principles and Related Human Disorders (2017)
  • Author(s): Fujiwara T
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 242 Issue: 2 Pages: 83-91
  • DOI: 10.1620/tjem.242.83
  • NAID: 130006776940
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed / Open Access
• [Journal Article] Impact of TET2 deficiency on iron metabolism in erythroblasts. (2017)
  • Author(s): Inokura K, Fujiwara T, Saito K, Iino T, Hatta S, Okitsu Y, Fukuhara N, Onishi Y, Ishizawa K, Shimoda K, Harigae H
  • Journal Title: Exp Hematol. Volume: - Pages: 56-67
  • DOI: 10.1016/j.exphem.2017.01.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] An Lysophosphatidic Acid Receptors 1 and 3 Axis Governs Cellular Senescence of Mesenchymal Stromal Cells and Promotes Growth and Vascularization of Multiple Myeloma. (2017)
  • Author(s): Kanehira M, Fujiwara T, Nakajima S, Okitsu Y, Onishi Y, Fukuhara N, Ichinohasama R, Okada Y, Harigae H.
  • Journal Title: Stem Cells. Volume: 35 Issue: 3 Pages: 739-753
  • DOI: 10.1002/stem.2499
  • Peer Reviewed
• [Journal Article] Identification of a novel putative mitochondrial protein FAM210B associated with erythroid differentiation. (2016)
  • Author(s): Kondo A, Fujiwara T, Okitsu Y, Fukuhara N, Onishi Y, Nakamura Y, Sawada K, Harigae H.
  • Journal Title: Int J Hematol. Volume: 103 Issue: 4 Pages: 387-395
  • DOI: 10.1007/s12185-016-1968-4
  • Peer Reviewed
• [Journal Article] Inhibition of human primary megakaryocyte differentiation by anagrelide: a gene expression profiling analysis. (2016)
  • Author(s): Sakurai K, Fujiwara T, Hasegawa S, Okitsu Y, Fukuhara N, Onishi Y, Yamada-Fujiwara M, Ichinohasama R, Harigae H.
  • Journal Title: Int J Hematol. Volume: 104 Issue: 2 Pages: 190-199
  • DOI: 10.1007/s12185-016-2006-2
  • Peer Reviewed
• [Journal Article] GATA2 regulates dendritic cell differentiation. (2016)
  • Author(s): Onodera K, Fujiwara T, Onishi Y, Itoh-Nakadai A, Okitsu Y, Fukuhara N, Ishizawa K, Shimizu R, Yamamoto M, Harigae H.
  • Journal Title: Blood Volume: 128 Issue: 4 Pages: 508-518
  • DOI: 10.1182/blood-2016-02-698118
  • Peer Reviewed / Open Access
• [Journal Article] Identification of a novel putative mitochondrial protein FAM210B associated with erythroid differentiation. (2016)
  • Author(s): Kondo A, Fujiwara T, Okitsu Y, Fukuhara N, Onishi Y, Nakamura Y, Sawada K, Harigae H.
  • Journal Title: International Journal of Hematology Volume: 未定
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Generation of Induced Pluripotent Stem Cell-Derived Erythroblasts From A Patient With X-Linked Sideroblastic Anemia (2017)
  • Author(s): Shunsuke Hatta, Tohru Fujiwara, Takako Yamamoto, Mayumi Kamata, Yoshiko Tamai, Yukiko Nakamura, Shin Kameoka, Hideo Harigae
  • Organizer: Seventh Congress of the International Biolron Society
  • Int'l Joint Research
• [Presentation] Exploring the Mechanism of Fog1-Dependent Transcriptional Regulation in Erythroid Cells (2017)
  • Author(s): Tohru Fujiwara, Katsuyuki Sasaki, Kei Saito, Shunsuke Hatta, Satoshi Ichikawa, Masahiro Kobayashi, Yoko Okitsu, Noriko Fukuhara, Yasushi Onishi, Hideo Harigae
  • Organizer: European Hematology Association 22nd Congress
  • Int'l Joint Research
• [Presentation] ALAS2遺伝子変異を認めた大球性鉄芽球性貧血の一例 (2017)
  • Author(s): 藤原亨、福原規子、猪俣美津恵、大西康、古山和道、張替秀郎
  • Organizer: 第41回日本鉄バイオサイエンス学会学術集会
• [Presentation] Exploring the mechanism of FOG1-dependent transcriptional regulation in erythroid cells (2017)
  • Author(s): Tohru Fujiwara, Katsuyuki Sasaki, Kei Saito, Shunsuke Hatta, Satoshi Ichikawa, Masahiro Kobayashi, Yoko Okitsu, Noriko Fukuhara, Yasushi Onishi, Hideo Harigae
  • Organizer: 第79回日本血液学会学術集会
• [Presentation] Transcription Factor Bach1 and Bach2 Operate Erythro-myeloid Competitive Differentiation by Responding to Environmental Changes. (2016)
  • Author(s): Kato H, Itoh-Nakadai A, Matsumoto M, Ebina-Shibuya R, Sato Y, Kobayashi M, Muto A, Fujiwara T, Harigae H, Igarashi K
  • Organizer: 第58回米国血液学会
  • Place of Presentation: サンディエゴ, アメリカ
  • Year and Date: 2016-12-02
  • Int'l Joint Research
• [Presentation] Generation of induced pluripotent stem cell-derived erythroblasts from a patient with X-linked sideroblastic anemia. (2016)
  • Author(s): Hatta S, Fujiwara T, Yamamoto T, Kamata M, Tamai Y, Nakamura Y, Kawamata S, Harigae H
  • Organizer: 第58回米国血液学会
  • Place of Presentation: サンディエゴ, アメリカ
  • Year and Date: 2016-12-02
  • Int'l Joint Research
• [Presentation] Identification of a novel putative mitochondrial protein FAM210B associated with erythroid differentiation. (2016)
  • Author(s): Kondo A, Fujiwara T, Okitsu Y, Fukuhara N, Onishi Y, Nakamura Y, Sawada K, Harigae H
  • Organizer: 第78回日本血液学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-10-13
• [Presentation] Transcriptional regulation of erythropoiesis. (2016)
  • Author(s): Fujiwara T
  • Organizer: 第78回日本血液学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-10-13
  • Invited
• [Presentation] 第78回日本血液学会 (2016)
  • Author(s): Saito K, Inokura K, Fujiwara T, Hatta S, Okitsu Y, Fukuhara N, Onishi Y, Ishizawa K, Shimoda K, Harigae H
  • Organizer: 第78回日本血液学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-10-13
• [Book] 今日の治療指針2017年度版―私はこうして治療している；鉄欠乏性貧血 (2017)
  • Author(s): 藤原 亨
  • Total Pages: 2000
  • Publisher: 医学書院
• [Book] 日本臨床：貧血学―最新の動向・治療動向―；鉄芽球性貧血 検査・診断・治療 (2017)
  • Author(s): 藤原 亨
  • Total Pages: 644
  • Publisher: 日本臨床社
• [Remarks] 東北大学 血液・免疫病学分野
  • URL: http://www.rh.med.tohoku.ac.jp/index.html
• [Remarks] 東北大学 血液免疫病学分野ホームページ
  • URL: http://www.rh.med.tohoku.ac.jp/index.html