Generation and analysis of in vitro, in vivo model of sideroblastic anemia
Project/Area Number |
26293225
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
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Research Institution | Tohoku University |
Principal Investigator |
Harigae Hideo 東北大学, 医学(系)研究科(研究院), 教授 (50302146)
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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)
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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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)
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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.
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Report
(4 results)
Research Products
(16 results)
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[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
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Journal Title
Exp Hematol.
Volume: -
Pages: -
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[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.
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Journal Title
Genet Med.
Volume: -
Pages: -
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[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.
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Journal Title
Haematologica
Volume: 102
Pages: 454-465
DOI
Related Report
Peer Reviewed
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[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 – 2015-08-30
Related Report
Invited
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[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
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