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Generation and analysis of in vitro, in vivo model of sideroblastic anemia

Research Project

Project/Area Number 26293225
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Hematology
Research InstitutionTohoku University

Principal Investigator

Harigae Hideo  東北大学, 医学(系)研究科(研究院), 教授 (50302146)

Co-Investigator(Renkei-kenkyūsha) KAWAMATA Shin  公益財団法人先端医療振興財団, 副事業統括 (00360842)
FUJIWARA Tohru  東北大学, 大学病院, 講師 (60333796)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywords内科学 / 内科
Outline of Final Research Achievements

Sideroblastic anemia is characterized by anemia with ring sideroblasts in the bone marrow. In order to develop a novel therapy for sideroblastic anemia, iPS cells were established from a patient of X-linked sideroblastic anemia (XLSA), which is caused by mutations of 5-aminolevulinate synthase (ALAS2) gene. The expression profiling of erythroblasts derived from XLSA iPS cells showed that the expression levels of globins and erythroid-specific transcription factors were decreased compared to those derived from control iPS cells. When XLSA derived iPS cells were co-cultured with stromal cells; aberrant mitochondrial iron deposition was detected by prussian blue staining and electron microscope analysis. In addition, XLSA model mouse has been generated by introducing mutations to the enhancer lesion of ALAS2 gene by CRISPR/CAS9 system. Mutant mice were anemic, and the expression level of ALAS2 of bone marrow was decreased. Iron metabolism and erythropoiesis are under investigation.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (16 results)

All 2017 2016 2015 2014

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [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

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [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

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Clinical utility of next-generation sequencing for inherited bone marrow failure syndromes.2017

    • Author(s)
      Muramatsu H, Okuno Y, Yoshida K, Shiraishi Y, Doisaki S, Narita A, Sakaguchi H, Kawashima N, Wang X, Xu Y, Chiba K, Tanaka H, Hama A, Sanada M, Takahashi Y, Kanno H, Yamaguchi H, Ohga S, Manabe A, Harigae H, Kunishima S, Ishii E, Kobayashi M, Koike K, Watanabe K, Ito E, Takata M, Yabe M, Ogawa S, Miyano S, Kojima S.
    • Journal Title

      Genet Med.

      Volume: - Issue: 7 Pages: 796-802

    • DOI

      10.1038/gim.2016.197

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Iron-heme-Bach1 axis is involved in erythroblast adaptation to iron deficiency.2017

    • Author(s)
      Kobayashi M, Kato H, Hada H, Itoh-Nakadai A, Fujiwara T, Muto A, Inoguchi Y, Ichiyanagi K, Hojo W, Tomosugi N, Sasaki H, Harigae H, Igarashi K.
    • Journal Title

      Haematologica

      Volume: 102 Issue: 3 Pages: 454-465

    • DOI

      10.3324/haematol.2016.151043

    • Related Report
      2016 Annual Research Report
    • 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

      Int J Hematol.

      Volume: 103 Issue: 4 Pages: 387-395

    • DOI

      10.1007/s12185-016-1968-4

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] Identification of a novel mitochondorial protein FAM210B associated with erythroid differentiation2016

    • Author(s)
      近藤愛子、藤原亨、沖津庸子、福原規子、大西康、中村幸夫、澤田賢一、張替秀郎
    • Organizer
      日本血液学会
    • Place of Presentation
      パシフィコ横浜・横浜市
    • Related Report
      2016 Annual Research Report
  • [Presentation] Impact of TET2 on iron metabolism in erythroblasts:A potential link to ring sidero formation2016

    • Author(s)
      斎藤慧、猪倉恭子、藤原亨、八田俊介、沖津庸子、福原規子、大西康、石澤賢一、下田和哉、張替秀郎
    • Organizer
      日本血液学会
    • Place of Presentation
      パシフィコ横浜・横浜市
    • Related Report
      2016 Annual Research Report
  • [Presentation] 腸管上皮細胞モデルにおけるALAの代謝2016

    • Author(s)
      斎藤慧、藤原亨、田中徹、張替秀郎
    • Organizer
      日本鉄バイオサイエンス学会
    • Place of Presentation
      名古屋大学豊田講堂・名古屋市
    • Related Report
      2016 Annual Research Report
  • [Presentation] Clinical and genetic characteristics of sideroblastic anemia2016

    • Author(s)
      張替秀郎
    • Organizer
      the 14th China National Congress of Hematology
    • Place of Presentation
      suzho jinji lake international convention center 上海・中国
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Generation of Induced Pluripotent Stem Cell-Derived Erythroblasts from a Patient with X-Linked Sideroblastic Anemia2016

    • Author(s)
      Shunsuke Hatta,Tohru Fujiwara, Takako Yamamoto, Mayumi Kamata, Yoshiko Tamai, Yukio Nakamura, Shin Kawamata, Hideo Harigae
    • Organizer
      58th Annual Meeting of American Sciety of Hematology
    • Place of Presentation
      SanDiego convention center サンディエゴ・米国
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 遺伝性鉄芽球性貧血の疫学と分子病態2015

    • Author(s)
      藤原亨、張替秀郎
    • Organizer
      第39回日本鉄バイオサイエンス学会学術集会
    • Place of Presentation
      岡山コンベンションセンター(岡山市)
    • Year and Date
      2015-08-29
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Exploring potential usefulness of 5-aminolevulinic acid for X-linked sideroblastic anemia2014

    • Author(s)
      Fujiwara T, Okamoto K, Niikuni R, Takahashi K, Okitsu Y, Fukuhara N, Onishi Y, Ishizawa K, Ichinohasama R, Nakamura Y, Nakajima M, Tanaka T, Harigae H
    • Organizer
      第56回アメリカ血液学会
    • Place of Presentation
      サンフランシスコ(米国)
    • Year and Date
      2014-12-06 – 2014-12-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Impact of TET2 deficiency on iron metabolism in erythropoiesis:a potential link to ring sideroblast formation2014

    • Author(s)
      Inokura K, Fujiwara T, Okitsu Y, Fukuhara N, Onishi Y, Ishizawa K, Shimoda K, Harigae H
    • Organizer
      第56回アメリカ血液学会
    • Place of Presentation
      サンフランシスコ(米国)
    • Year and Date
      2014-12-06 – 2014-12-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Exploring the potential usefulness of 5-aminolevulinic acid (ALA) for sideroblastic anemia2014

    • Author(s)
      Nikuni R, Fujiwara T, Okitsu Y, Fukuhara N, Onishi Y, Ishizawa K, Ichinohasama R, Tanaka T, Harigae H
    • Organizer
      第76回日本血液学会
    • Place of Presentation
      大阪国際会議場(大阪府)
    • Year and Date
      2014-10-31 – 2014-11-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] 鉄芽球性貧血に対するALAの有用性の基礎的検討2014

    • Author(s)
      藤原亨、新國僚祐、田中徹、張替秀郎
    • Organizer
      第38回日本鉄バイオサイエンス学会学術集会
    • Place of Presentation
      仙台国際センター(仙台市)
    • Year and Date
      2014-09-06 – 2014-09-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] TET2遺伝子の鉄芽球性貧血発症への関与2014

    • Author(s)
      猪倉恭子、藤原亨、下田和哉、張替秀郎
    • Organizer
      第38回日本鉄バイオサイエンス学会学術集会
    • Place of Presentation
      仙台国際センター(仙台市)
    • Year and Date
      2014-09-06 – 2014-09-07
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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