Direct reprogramming of hematopoietic cells into hematopoietic stem cells

• Project/Area Number: 23659483
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Chiba University
• Principal Investigator: IWAMA Atsushi 千葉大学, 大学院・医学研究院, 教授 (70244126)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ダイレクトリプログラミング / 造血幹細胞

Research Abstract

Direct reprogramming of somatic cells into hematopoietic stem cells is challenging and has not been yet achieved. In this study, I tried to reprogram an E2A-deficient pro-B cell line, which retain multipotent differentiation capacity, into hematopoietic stem cells. Various combinations of key transcription factors known to be essential for hematopoietic stem cells were transduced into E2A-deficient pro-B cells and cultured on stromal cells in a medium which supports hematopoietic stem cells. I observed generation of myeloid cells expanding in culture, but failed to obtain hematopoietic stem cells in this trial. To achieve the real reprogramming, more technical renovation is definitely needed.

Research Products

• [Journal Article] Role of SOX17 in hematopoietic development from human embryonic stem cells. (2013)
  • Author(s): Nakajima-Takagi Y, Osawa M, Oshima M, Takagi H, Miyagi S, Endoh M, Endo TA, Takayama N, Eto K, Toyoda T, Koseki H, Nakauchi H, and Iwama A.
  • Journal Title: Blood Volume: 121 Pages: 447-458
  • Peer Reviewed
• [Journal Article] RUNX1/AML1 mutant collaborates with BMI1 overexpression in the development of human and murine myelodysplastic syndromes. (2013)
  • Author(s): Harada Y, Inoue D, Ding Y, Imagawa J, Doki N, Matsui H, Yahata T, Matsushita H, Ando K, Sashida G, Iwama A, Kitamura T, and Harada H.
  • Journal Title: Blood Volume: 121 Pages: 3434-3446
  • Peer Reviewed
• [Journal Article] 「幹細胞老化とエピジェ ネティクス」アンチ・エイジング医学 (2013)
  • Author(s): 岩間 厚志
  • Journal Title: 日本抗加齢医学会雑誌 Volume: 9(1)
• [Journal Article] Epigenetics of hematopoiesis and hematological malignancies. (2012)
  • Author(s): Iwama A.
  • Journal Title: Int J Hematol Volume: 96 Pages: 403-404
• [Journal Article] Epigenetic regulation of hematopoiesis. (2012)
  • Author(s): Sashida G and Iwama A.
  • Journal Title: Int J Hematol Volume: 96 Pages: 405-412
  • Peer Reviewed
• [Journal Article] Ezh2 augments leukemogenecity by reinforcing differentiation blockage in acute myeloid leukemia. (2012)
  • Author(s): Tanaka S, Miyagi S, Sashida G, Chiba T, Yuan J, Mochizuki-Kashio M, Suzuki Y, Sugano S, Nakaseko C, Yokote K, Koseki H, and Iwama A.
  • Journal Title: Blood Volume: 120 Pages: 1107-1117
  • Peer Reviewed
• [Journal Article] Circulating soluble LR11/SorLA levels are highly increased and ameliorated by chemotherapy in acute leukemias. (2012)
  • Author(s): Sakai S, Nakaseko C, Takeuchi M, Ohwada C, Shimizu N, Tsukamoto S, Kawaguchi T, Jiang M, Sato Y, Ebinuma H, Yokote K, Iwama A, Fukamachi I, Schneider WJ, Saito Y, and Bujo H.
  • Journal Title: Clinica Chemica Acta Volume: 413 Pages: 1542-1548
  • Peer Reviewed
• [Journal Article] TET2 is essential for survival and hematopoietic stem cellhomeostasis. (2012)
  • Author(s): Shide K, Kameda T, Shimoda H, Yamaji T, Abe H, Kamiunten A, Sekine M, Hidaka T, Katayose K, Kubuki Y, Yamamoto S, Miike T, Iwakiri H, Hasuike S, Nagata K, Iwama A, Matsuda T, Kitanaka A and Shimoda K.
  • Journal Title: Leukemia Volume: 26 Pages: 2216-2223
  • Peer Reviewed
• [Journal Article] New approaches to expand hematopoietic stem and progenitor cells. (2012)
  • Author(s): Nishino T, Osawa M, and Iwama A.
  • Journal Title: Expert Opin Biol Ther Volume: 12 Pages: 743-756
  • Peer Reviewed
• [Journal Article] Bmi1 confers resistance to oxidative stress on hematopoietic stem cells. (2012)
  • Author(s): Nakamura S, Oshima M, Yuan J, Saraya A, Miyagi S, Konuma T, Yamazaki S, Osawa M, Nakauchi H, Koseki H, and Iwama A.
  • Journal Title: PLoS ONE Volume: 7
  • Peer Reviewed
• [Journal Article] Lethal myelofibrosis induced by Bmi1-deficient hematopoietic cells unveils a tumor suppressor function of the polycomb group genes. (2012)
  • Author(s): Oguro H, Yuan J, Tanaka S, Miyagi S, Mochizuki-Kashio M, Ichikawa H, Yamazaki S, Koseki H, Nakauchi H, and Iwama A.
  • Journal Title: J Exp Med Volume: 209 Pages: 445-454
  • Peer Reviewed
• [Journal Article] 「癌幹細胞とエピゲノム制御異常」 (2012)
  • Author(s): 指田吾郎、千葉哲博、岩間厚志
  • Journal Title: 細胞工学 Volume: 31 Pages: 24-31
• [Presentation] Critical role of SOX17 in hematopoietic development from human embryonic stem cells (2013)
  • Author(s): Osawa M, Nakajima Y, Oshima M, Takagi H, Iwama A.
  • Organizer: CiRA International Symposium
  • Place of Presentation: Kyoto,Japan(oral)
• [Presentation] 「MDS発症におけるポリコーム遺伝子EZH2の」関 与」 (2013)
  • Author(s): 武藤朋也, 岩間厚志
  • Organizer: 第17回造血器腫瘍研究会兼、がん研究 開発費「がん幹細胞に対する新規分子法的治 療薬の開発を目指した基盤研究」班会議
  • Place of Presentation: 宮崎(オーラル)
• [Presentation] Critical role of SOX17 in hematopoietic development from human embryonic stem cells (2013)
  • Author(s): Osawa M, Nakajima Y, Oshima M, Takagi H, Iwama A.
  • Organizer: Keystone Symposium : Hematopoiesis
  • Place of Presentation: Corolado, U.S.A (poster)
• [Presentation] 胎生期の造血幹細胞と成体の造血幹細胞とでは、ポリコーム遺伝子Ezh2への依存性が異なる (2012)
  • Author(s): 望月牧子、岩間厚志
  • Organizer: 第8回麒麟塾
  • Place of Presentation: 東京(オーラル)
  • Year and Date: 2012-07-07
• [Presentation] Hbo1-Brd1/Brpf2複合体は、H3K14のローバルなアセチル化を引き起こし、胎生期肝における赤血球造血に必須である」 (2012)
  • Author(s): 宮城聡、岩間厚志
  • Organizer: 第8回麒麟塾
  • Place of Presentation: 東京(オーラル)
  • Year and Date: 2012-07-07
• [Presentation] 「ヒストン修飾による造血幹細胞の機能制御」シンポジウム「幹細胞の転写制御、エピジェネティック制御」 (2012)
  • Author(s): 岩間厚志
  • Organizer: 第33回日本炎症・再生医学会
  • Place of Presentation: 福岡(オーラル)
  • Year and Date: 2012-07-05
• [Presentation] Role of the polycomb group proteins in the maintenance of hematopoietic stem cells and restriction of tumor development (2012)
  • Author(s): Iwama A.
  • Organizer: IMSUT & RCAST Global COE Program Mini-Symposium
  • Place of Presentation: Tokyo,Japan(Oral)
  • Year and Date: 2012-06-18
• [Presentation] Loss of Ezh2 promotes the development of mutant-RUNX1 induced MDS (2012)
  • Author(s): Sashida G, Tanaka S, Mochizuki-Kashio M, Saraya A, Muto T, Iwama A.
  • Organizer: 54^<th> ASH Annual Meeting and Exposition
  • Place of Presentation: Atlanta, U.S.A. (Oral)
• [Presentation] Long-Term cell automomous effect of Tet2 loss in hematopoietic cells in mice (2012)
  • Author(s): Muto T, Sashida G, Oshima M, Nakaseko C, Yokote K, Shimoda K, Iwama A
  • Organizer: 54^<th> AHS Annual Meeting and Exposition
  • Place of Presentation: Atlanta, U.S.A.(Poster)
• [Presentation] Role of the polycomb group proteins in the maintenance of hematopoietic stem cells and restriction of tumor development (2012)
  • Author(s): Iwama A.
  • Organizer: The 74^<th> Annual Meeting of the Japanese Society of Hematology.
  • Place of Presentation: Kyoto, Japan(Oral)
• [Presentation] The role of long intergenic non-coding RNAs in hematopoietic stem cells (2012)
  • Author(s): Wendt G, Iwama A
  • Organizer: The 74th Annual Meeting of the Japanese Society of Hematology.
  • Place of Presentation: Kyoto, Japan (Poster)
• [Presentation] Radiation effects on human HSPCs in vivo (2012)
  • Author(s): Wang C, Nakamura S, Kusunoki Y, Kyoizumi S, Imai K, Nakachi K, Iwama A
  • Organizer: The 74^<th> Annual Meeting of the Japanese Society ofHematology.
  • Place of Presentation: Kyoto, Japan (Poster)
• [Presentation] ヒトES細胞からの造血細胞分化におけるSOX17の役割 (2012)
  • Author(s): 中島やえ子、岩間厚志
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都(オーラル)
• [Presentation] Role of the polycomb group proteins in the maintenance of hematopoietic stem cells and restriction of tumor development (2012)
  • Author(s): Iwama A.
  • Organizer: 41^<st> Annual Scientific Meeting of the ISEH.
  • Place of Presentation: Amsterdam, Netherlands(Oral)
• [Presentation] Profiling of long intergenic non-coding RNAs in hematopoietic stem cells (2012)
  • Author(s): Wendt G, I wama A
  • Organizer: 41^<st> Annual Scientific Meeting of the ISEH.
  • Place of Presentation: Amsterdam, Netherlands(Poster)
• [Presentation] Inhibition of TGF-BETA signaling in the early mesoderm stage promotes the development of hematopoietic progenitors from human embryonic stem cells (2012)
  • Author(s): Osawa M, Takagi H, Nakajima Y, Endoh M, Endo T, Iwama A
  • Organizer: ISSCR 10^<th> Annual Meeting.
  • Place of Presentation: Yokohama,Japan(Poster)
• [Presentation] The critical role of SOX17 in the development of early hematopoietic progenitors from human embryonic stem cells (2012)
  • Author(s): Nakajima-Takagi Y, Osawa M, Oshima M, Takagi H, Iwama A
  • Organizer: ISSCR the 10^<th> Annual Meeting.
  • Place of Presentation: Yokohama,Japan(Poster)
• [Presentation] Bmil confers resistance to oxidative stress on hematopoietic stem cells (2012)
  • Author(s): Oshima M, Nakamura S, Saraya A, Miyagi S, Koseki H, Iwama A
  • Organizer: ISSCR the 10^<th> Annual Meeting.
  • Place of Presentation: Yokohama,Japan(Poster)
• [Presentation] Lethal myelofibrosis induced by Bmi1-deficient hematopoietic cells unveils a tumor suppressor function of the polycomb group genes (2012)
  • Author(s): Iwama A.
  • Organizer: The 10^<th> Stem Cell Research Symposium.
  • Place of Presentation: Awaji,Japan(Oral)
• [Presentation] Critical role of SOX17 in the hematopoietic development from human embryonic stem cells (2012)
  • Author(s): Osawa M, Nakajima Y, Oshima M, Takagi H, Endoh M, Endo T, Iwama A
  • Organizer: The 10^<th> Stem Cell Research Symposium.
  • Place of Presentation: Awaji,Japan(Oral)
• [Presentation] ヒト造血幹細胞の体外増幅の可能性 (2012)
  • Author(s): 岩間厚志
  • Organizer: 第34回日本造血細胞移植学会総会
  • Place of Presentation: 大阪
• [Book] 「幹細胞のエピジェネティクス」「再生医療叢書1幹細胞」(山中伸弥、中内啓光編) (2012)
  • Author(s): 岩間厚志
  • Publisher: 朝倉書店
• [Book] 「白血病幹細 胞におけるエピジェネティクス制御」「造血 器腫瘍とエピジェネティクス」(木崎昌弘編) (2012)
  • Author(s): 指田吾郎、岩間 厚志
  • Publisher: 医薬ジャーナル
• [Book] 「造血幹細胞」「みんな (2012)
  • Author(s): 岩間厚志
  • Publisher: 医薬ジャーナル社
• [Book] 造血幹細胞のエピジェ ネティクス」Annual Review 血液(高久史麿、小澤敬也、坂田洋一、金倉譲、小島勢二編)
  • Author(s): 岩間厚志
  • Publisher: 中外医学
• [Remarks]
  • URL: http://www.m.chiba-u.ac.jp/class/molmed/index.html