Elucidating the mechanism of genome-wide transcriptional repression in hematopoietic stem cell development

• Project/Area Number: 26461454
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kumamoto University (2015-2016); Juntendo University (2014)
• Principal Investigator: Yokomizo Tomomasa 熊本大学, 国際先端医学研究機構, 特定事業研究員 (80590314)
• Co-Investigator(Renkei-kenkyūsha): MORI Seiichi がん研究会, がん研究所, 主任研究員 (10334814)
• Research Collaborator: IIZUKA Kazuhide 順天堂大学, 医学部
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 造血発生 / 造血幹細胞

Outline of Final Research Achievements

The aim of this study is to understand how hematopoietic stem cells (HSCs) are generated during mouse development. Especially we focused on how stemness is obtained after the specification of hematopoietic cells. Our study revealed that total amount of mRNA, cell size and surface marker expressions (CD71 and CD98) decrease during the HSC generation, suggesting that mTOR signaling might be involved in this process. These results could be applied to develop a new culture system for in vitro HSC generation.

Research Products

• [Journal Article] Runx Family Genes in Tissue Stem Cell Dynamics. (2017)
  • Author(s): Wang CQ, Mok MM, Yokomizo T, Tergaonkar V, Osato M.
  • Journal Title: Adv Exp Med Biol. Volume: 962 Pages: 117-138
  • DOI: 10.1007/978-981-10-3233-2_9
  • ISBN: 9789811032318, 9789811032332
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Lack of Phenotypical and Morphological Evidences of Endothelial to Hematopoietic Transition in the Murine Embryonic Head during Hematopoietic Stem Cell Emergence. (2016)
  • Author(s): Iizuka K, Yokomizo T, Watanabe N, Tanaka Y, Osato M, Takaku T, Komatsu N.
  • Journal Title: PLoS One Volume: 11 Issue: 5 Pages: e0156427-e0156427
  • DOI: 10.1371/journal.pone.0156427
  • Peer Reviewed / Open Access
• [Journal Article] Functional and molecular characterization of mouse Gata2-independent hematopoietic progenitors. (2016)
  • Author(s): Kaimakis P, de Pater E, Eich C, Solaimani Kartalaei P, Kauts ML, Vink CS, van der Linden R, Jaegle M, Yokomizo T, Meijer D, Dzierzak E.
  • Journal Title: Blood Volume: 127 Issue: 11 Pages: 1426-1437
  • DOI: 10.1182/blood-2015-10-673749
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] RUNX1 haploinsufficiency results in granulocyte colony-stimulating factor hypersensitivity. (2016)
  • Author(s): Chin DW, Sakurai M, Nah GS, Du L, Jacob B, Yokomizo T, Matsumura T, Suda T, Huang G, Fu XY, Ito Y, Nakajima H, Osato M.
  • Journal Title: Blood Cancer J. Volume: 6 Issue: 1 Pages: e379-e379
  • DOI: 10.1038/bcj.2015.105
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Cellular heterogeneity of hematopoietic clusters in the mouse embryo (2016)
  • Author(s): Tomomasa Yokomizo
  • Organizer: Hematopoietic stem cell researchers symposium at IMS
  • Place of Presentation: 東京大学医科学研究所
  • Year and Date: 2016-09-09
  • Invited
• [Presentation] Whole-mount three-dimensional analysis of hematopoietic development in the mouse embryonic head (2016)
  • Author(s): Yokomizo T, Iizuka K, Watanabe N, Tanaka Osato M, Takaku T, Komatsu N
  • Organizer: JSPS-NUS Joint Symposium
  • Place of Presentation: Singapore (Singapore)
  • Year and Date: 2016-01-14
  • Int'l Joint Research
• [Presentation] Highly efficient Runx1 enhancer eR1-mediated genetic engineering for fetal and adult hematopoietic stem cells (2015)
  • Author(s): Osato M, Koh CP, Yokomizo T
  • Organizer: 13th Stem Cell Symposium
  • Place of Presentation: University of Tokyo (Tokyo, Japan)
  • Year and Date: 2015-05-29
  • Int'l Joint Research