Molecular analysis of fetal hematopoiesis using culture system with ES cells

• Project/Area Number: 25670489
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Embryonic/Neonatal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: EBIHARA Yasuhiro 東京大学, 医科学研究所, 助教 (40302608)
• Co-Investigator(Kenkyū-buntansha): MOCHIZUKI Shinji 東京大学, 医科学研究所, 特任助教 (90349473) ; OTSU Makoto 東京大学, 医科学研究所, 准教授 (30361330)
• Project Period (FY): 2013-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: 胎児医学 / ES細胞

Research Abstract

We developed the culture system to generate human hematopoietic stem/progenitor cells from human embryonic stem cells (hESCs) more physiologically by the coculture with autologous stromal cells derived from hESCs. In this study, we analyzed fetal hematopoiesis using our culture system.
We revealed that the established stromal cells were derived from mesodermal mesenchymal stem cells (MSCs). Human ESC-derived MSCs described above retained the ability to support the growth of autologous hESCs similar to MEF. And our system was capable of generating a number of adult-type human hematopoietic stem/progenitor cells. Using our coculture system may be available for further analysis of human fetal hematopoiesis.

Research Products

• [Journal Article] Impact of sex incompatibility on the outcome of single-unit cord blood transplantation for adult patients with hematological malignancies. (2014)
  • Author(s): Konuma T, Tojo A, et al.
  • Journal Title: Bone Marrow Transplant. Volume: 49 Issue: 5 Pages: 634-9
  • DOI: 10.1038/bmt.2014.10
  • Peer Reviewed / Open Access
• [Journal Article] Allogeneic stem cell transplantation for patients with acute myeloid leukemia developing from severe congenital neutropenia. (2014)
  • Author(s): Ebihara Y, Ishikawa K, Mochizuki S, Tanaka R, Manabe A, Iseki T, Maekawa T, Tsuji K.
  • Journal Title: Br J Haematol. Volume: 164 Issue: 3 Pages: 451-464
  • DOI: 10.1111/bjh.12638
  • Peer Reviewed / Open Access
• [Journal Article] Effect of ABO Blood Group Incompatibility on the Outcome of Single-Unit Cord Blood Transplantation after Myeloablative Conditioning (2014)
  • Author(s): Konuma T, Tojo A, et al.
  • Journal Title: Biol Blood Marrow Transplant. Volume: 20 Issue: 4 Pages: 577-581
  • DOI: 10.1016/j.bbmt.2013.12.563
  • Peer Reviewed / Open Access
• [Journal Article] Acquired deficiency of A20 results in rapid apoptosis, systemic inflammation, and abnormal hematopoietic stem cell function. (2014)
  • Author(s): Nagamachi A, Nakata Y, Ueda T, Yamasaki N, Ebihara Y, Tsuji K, Honda Zi, Takubo K, Suda T, Oda H, Inaba T, Honda H
  • Journal Title: PLos One Volume: 9 Issue: 1 Pages: 1-10
  • DOI: 10.1371/journal.pone.0087425
  • Peer Reviewed / Open Access
• [Journal Article] Single-Unit Cord Blood Transplantation after Granulocyte Colony-Stimulating Factor-Combined Myeloablative Conditioning for Myeloid Malignancies Not in Remission. (2014)
  • Author(s): Konuma T, Tojo A, et al.
  • Journal Title: Biol Blood Marrow Transplant. 20(3): Volume: 20 Issue: 3 Pages: 396-401
  • DOI: 10.1016/j.bbmt.2013.12.555
  • Peer Reviewed
• [Journal Article] Pneumothorax in an early phase after allogeneic hematopoietic stem cell transplantation. (2013)
  • Author(s): Ebihara Y, Tojo A, et al.
  • Journal Title: Hematol Rep. Volume: 5 Issue: 2 Pages: 34-35
  • DOI: 10.4081/hr.2013.e10
  • Peer Reviewed
• [Journal Article] Unusual extramedullary relapse after haploidentical bone marrow transplantation in a patient with acute lymphoblastic leukemia. (2013)
  • Author(s): Ebihara Y, Yamamoto S, Mochizuki S, Tsukada M, Taya Y, Sato A, Kawakita T, Kato S, Ooi J, Takahashi S, Tojo A, Tsuji K.
  • Journal Title: J Blood Disorders Transf Volume: 4 Issue: 05 Pages: 155-155
  • DOI: 10.4172/2155-9864.1000155
  • Peer Reviewed
• [Journal Article] Generation of engraftable hematopoietic stem cells from induced pluripotent stem cells by way of teratoma formation. (2013)
  • Author(s): Suzuki N, Yamazaki S, Yamaguchi T, Okabe M, Masaki H, Takaki S, Otsu M, Nakauchi H.
  • Journal Title: Mol Ther. Volume: 21 Issue: 7 Pages: 1424-31
  • DOI: 10.1038/mt.2013.71
  • Peer Reviewed
• [Journal Article] Top-down motif engineering of a cytokine receptor for directing ex vivo expansion of hematopoietic stem cells. (2013)
  • Author(s): Saka K, Kawahara M, Teng J, Otsu M, Nakauchi H, Nagamune T.
  • Journal Title: J Biotechnol. Volume: 168 Issue: 4 Pages: 659-65
  • DOI: 10.1016/j.jbiotec.2013.09.012
  • Peer Reviewed
• [Journal Article] Generation of Col2a1-EGFP iPS cells for monitoring chondrogenic differentiation (2013)
  • Author(s): Saito T, Yano F, Mori D, Ohba S, Hojo H, Otsu M, Eto K, Nakauchi H, Tanaka S, Chung UI, Kawaguchi H
  • Journal Title: PLoS One Volume: 16;8(9) Issue: 9 Pages: e74137-e74137
  • DOI: 10.1371/journal.pone.0074137
  • Peer Reviewed
• [Journal Article] Profiling of MicroRNA in Human and Mouse ES and iPS Cells Reveals Overlapping but Distinct MicroRNA Expression Patterns. (2013)
  • Author(s): Razak SR, Ueno K, Takayama N, Nariai N, Nagasaki M, Saito R, Koso H, Lai CY, Murakami M, Tsuji K, Michiue T, Nakauchi H, Otsu M, Watanabe S.
  • Journal Title: PLoS One. Volume: 8 Issue: 9 Pages: e73532-e73532
  • DOI: 10.1371/journal.pone.0073532
  • Peer Reviewed / Open Access
• [Journal Article] Adipose natural regulatory B cells negatively control adipose tissue inflammation (2013)
  • Author(s): Nishimura S, Manabe I, Takaki S, Nagaskai M, Ostu M, Yamashita H, Sugita J, Yoshimura K, Eto K, Komuro I, Kadowaki T, Nagai R
  • Journal Title: Cell Metabolism Volume: 18 Issue: 5 Pages: 759-766
  • DOI: 10.1016/j.cmet.2013.09.017
  • Peer Reviewed
• [Journal Article] ACTN1 Mutations Cause Congenital Macrothrombocytopenia (2013)
  • Author(s): 國島伸治、吉田健一
  • Journal Title: Am J Hum Genet Volume: 92 Issue: 3 Pages: 431-438
  • DOI: 10.1016/j.ajhg.2013.01.015
  • Peer Reviewed
• [Journal Article] Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms. (2013)
  • Author(s): Kon A, Yoshida K
  • Journal Title: Nature Genet. Volume: 45 Issue: 10 Pages: 1232-1237
  • DOI: 10.1038/ng.2731
  • Peer Reviewed
• [Journal Article] Immortalization of Erythroblasts by c-MYC and BCL-XL Enables Large-Scale Erythrocyte Production from Human Pluripotent Stem Cells. (2013)
  • Author(s): Hirose, S., N. Takayama, S. Nakamura, K. Nagasawa, K. Ochi, S. Hirata, S. Yamazaki, T. Yamaguchi, M. Otsu, S. Sano, N. Takahashi, A. Sawaguchi, M. Ito, T. Kato, H. Nakauchi, and K. Eto.
  • Journal Title: Stem Cell Reports Volume: 1 Issue: 6 Pages: 499-508
  • DOI: 10.1016/j.stemcr.2013.10.010
  • NAID: 120005350227
  • Peer Reviewed
• [Journal Article] CAMT-iPS Cells Exhibiting Defective MPL Signaling Dysregulate Megakaryopoiesis and Erythropoiesis. (2013)
  • Author(s): Shinji Hirata, Naoya Takayama,Ryoko Jono-Ohnishi, Hiroshi Endo, Sou Nakamura, Takeaki Dohda, Masanori Nishi, Yuhei Hamazaki, Ei-ichi Ishii, Shin Kaneko, Makoto Otsu, Hiromitsu Nakauchi, Shinji Kunishima, and Koji Eto.
  • Journal Title: J Clin Invest. Volume: 123 Issue: 9 Pages: 3802-14
  • DOI: 10.1172/jci64721
  • Peer Reviewed
• [Journal Article] Generation of transgenic mouse line expressing Kusabira Orange throughout body, including erythrocytes, by random segregation of provirus method (2013)
  • Author(s): Hamanaka S, Ooehara J, Morita Y, Ema H, Takahashi S, Miyawaki A, Otsu M, Yamaguchi T, Onodera M, Nakauchi H
  • Journal Title: Biochem Biophys Res Commun Volume: i435(4) Issue: 4 Pages: 586-91
  • DOI: 10.1016/j.bbrc.2013.05.017
  • Peer Reviewed
• [Journal Article] Stem cell therapy: an exercise in patience and prudence. (2012)
  • Author(s): Lin HT, Otsu M, Nakauchi H.
  • Journal Title: Philos Trans R Soc Lond B Biol Sci Volume: 5 Issue: 1609 Pages: 20110334-20110334
  • DOI: 10.1098/rstb.2011.0334
  • Peer Reviewed
• [Presentation] 自己骨髄由来間葉系幹細胞を用いた血友病関節症に対する治療の可能性 (2013)
  • Author(s): 海老原康博, 望月慎史, 大津真, 竹谷英之, 辻浩一郎
  • Organizer: 第55回日本小児血液・がん学会学術集会
  • Place of Presentation: ヒルトン福岡シーホーク, 福岡
• [Presentation] 本邦におけるボルテゾミブ併用化学療法を行った小児再発難治性急性リンパ性白血病 24例の後方視的検討 (2013)
  • Author(s): 望月慎史, 小川千登世, 佐野秀樹, 木下明俊, 篠田邦大, 宮下恵実子, 吉原宏樹, 井口晶裕, 吉田咲子, 西川拓朗, 西眞範, 豊田秀実, 熊本忠史, 中村和洋, 西内律雄, 菊田敦 , 後藤裕明, 足立壮一, 水谷修紀
  • Organizer: 第55回日本小児血液・がん学会学術集会
  • Place of Presentation: ヒルトン福岡シーホーク, 福岡
• [Presentation] ヒトiPS由来肥満細胞の機能解析 (2013)
  • Author(s): 五十嵐晃, 熊谷智明, 平井博之, 永田欽也, 花田佐智代, 海老原康博, 辻浩一郎
  • Organizer: 第63回日本アレルギー学会
  • Place of Presentation: ホテルニューオータニ, 東京
• [Presentation] Drug screening for the 8p11 myeloproliferative syndrome using patient iPS cells (2013)
  • Author(s): Mai Nanya, Shohei Yamamoto, Yasuhiro Ebihara, Shinji Mochizuki, Makoto Otsu, Minoru Tozuka, Hiromitsu Nakauchi, Kohichiro Tsuji
  • Organizer: 第75回日本血液学会
  • Place of Presentation: ロイトン札幌, 札幌
• [Presentation] Generation and analysis of a novel model for CMML with acquired expression of CBL Q367P (2013)
  • Author(s): Yuichiro Nakata,Takeshi Ueda, Norimasa Yamasaki,Akiko Nagamachi, Keiyo Takubo,Yasuhiro Ebihara, Masashi Sanada, Seishi Ogawa, Kohichiro Tsuji,Toshio Suda,Toshiya Inaba, Hiroaki Honda
  • Organizer: 第75回日本血液学会
• [Presentation] 重症先天性好中球減少症患者由来のiPS細胞の樹立とその分子生物学的解析 (2013)
  • Author(s): 海老原康博, 平本貴史, 山本将平, 望月慎史, 辻浩一郎, 溝口洋子, 中村和洋, 小林正夫
  • Organizer: 第116回日本小児科学会
  • Place of Presentation: 広島国際会議場, 広島
• [Presentation] 重症先天性好中球減少症患者由来のiPS細胞の樹立とその分子生物学的解析 (2013)
  • Author(s): 海老原康博、平本貴史、山本将平、望月慎史、辻浩一郎、溝口洋子、中村和洋、小林正夫
  • Organizer: 第116回日本小児科学会
  • Place of Presentation: 広島：広島国際会議場
• [Presentation] Drug screening for the 8p11 myeloproliferative syndrome using patient iPS cells (2013)
  • Author(s): Mai Nanya, Shohei Yamamoto, Yasuhiro Ebihara, Shinji Mochizuki, Makoto Otsu, Minoru Tozuka, Hiromitsu Nakauchi, Kohichiro Tsuji
  • Organizer: 第75回日本血液学会
  • Place of Presentation: 札幌：ロイトン札幌
• [Presentation] Generation and analysis of a novel model for CMML with acquired expression of CBL Q367P (2013)
  • Author(s): Yuichiro Nakata，Takeshi Ueda，Norimasa Yamasaki，Akiko Nagamachi，Keiyo Takubo，Yasuhiro Ebihara，Masashi Sanada, Seishi Ogawa, Kohichiro Tsuji，Toshio Suda，Toshiya Inaba, Hiroaki Honda
  • Organizer: 第75回日本血液学会
  • Place of Presentation: 札幌：ロイトン札幌
• [Presentation] ヒトiPS由来肥満細胞の機能解析 (2013)
  • Author(s): 五十嵐晃、熊谷智明、平井博之、永田欽也、花田佐智代、 海老原康博、辻浩一郎
  • Organizer: 第63回日本アレルギー学会
  • Place of Presentation: 東京：ホテルニューオータニ
• [Presentation] 自己骨髄由来間葉系幹細胞を用いた血友病関節症に対する治療の可能性 (2013)
  • Author(s): 海老原康博、望月慎史、大津真、竹谷英之、辻浩一郎
  • Organizer: 第55回日本小児血液・がん学会学術集会
  • Place of Presentation: 福岡：ヒルトン福岡シーホーク
• [Presentation] 本邦におけるボルテゾミブ併用化学療法を行った小児再発難治性急性リンパ性白血病 24 例 の後方視的検討 (2013)
  • Author(s): 望月慎史、小川千登世、佐野秀樹、木下明俊、篠田邦大、宮下恵実子、吉原宏樹、井口晶裕、吉田咲子、西川拓朗、西眞範、豊田秀実、熊本忠史、中村和洋、西内律雄、菊田敦、後藤裕明、足立壮一、水谷修紀
  • Organizer: 第55回日本小児血液・がん学会学術集会
  • Place of Presentation: 福岡：ヒルトン福岡シーホーク
• [Remarks] 東京大学医科学研究所 幹細胞治療研究センター幹細胞プロセシング分野
  • URL: http://stemcell-u-tokyo.org/scp/