Koji Eto, M.D., Ph.D. Professor
Multicellular organisms are generated by asymmetric division to produce various cell types. By asymmetric division, hematopoietic stem/progenitor cells undergo self-renewal and differentiation to produce many types of cells to supply blood cells for a lifetime. By elucidating the molecular mechanism of this phenomenon, we have established technologies to induce hematopoietic progenitor cells, platelets and various other blood cells from human pluripotent stem cells. We will promote basic research and technology improvement for the realization of gene therapy and a blood transfusion system that does not depend on blood donation.
Research and EducationRecapitulating the development of hematopoietic stem cells, megakaryocytes and erythroblasts from iPS cells have not been completely successful. We are conducting basic research to clarify the mechanism of human hematopoiesis. In addition, to efficiently produce safel platelets from iPS cells for clinical application, megakaryocyte cell lines were established and new compounds and bioreactors were developed through joint research with engineering researchers and chemical companies. In the future, we aim to supply a versatile preparation for patients who do not have the necessary platelet products available, and to develop platelets for treatments of bone fractures and bacterial infections.
Lab members decide their working hours by themselves, and based on their inner scientific curiosity, always ask “why” and proceed with research to transmit their own achievements to the world. In addition, we discuss experimental results with lab members, participate in the weekly English presentation and journal club to brush up our research ability, and through the happy hour, interact with various members of the lab including foreign students.
In human bone marrow, hematopoietic stem cells differentiate and mature into megakaryocytes through stimulation of various humoral factors and dramatic changes in physical and chemical conditions. These mature megakaryocytes extend their cytoplasm into the lumen of blood vessels and release large amounts of platelets by blood flow. By observing the environment in the human body, developing new materials and equipment and further simulating physical conditions, the bone marrow condition is recapitulated outside the body, aiming at the industrialization of platelet production.
Lab group photo
- Seo H, Chen SJ, Hashimoto K, Endo H, Nishi Y, Ohta A, Yamamoto T, Hotta A, Akira Sawaguchi A, Hayashi H, Koseki N, Murphy GJ, Fukuda K, Sugimoto N, Eto K. A β1-tubulin-based megakaryocyte maturation reporter system identifies novel drugs that promote platelet production. Blood Advances. 2(17):2262-2272, 2018. Doi: 10.1182/bloodadvances.2018019547.
- Ito Y, Nakamura S, Sugimoto N, Shigemori T, Kato Y, Ohno M, Sakuma S, Ito K, Kumon H, Hirose H, Okamoto H, Nogawa M, Iwasaki M, Kihara S, Fujio K, Matsumoto T, Higashi N, Hashimoto K, Sawaguchi A, Harimoto KI, Nakagawa M, Yamamoto T, Handa M, Watanabe N, Nishi E, Arai F, Nishimura S, Eto K. Turbulence activates platelet biogenesis to enable clinical scale ex vivo production. Cell 174(3):636-648. E19. Doi: 10.1016/j.cell.2018.06.011. Epub 2018 Jul 12.
- Aihara A, Koike T, Abe N, Nakamura S, Sawaguchi A, Nakamura T, Sugimoto N, Nakauchi H, Nishino T, Eto K. Novel TPO receptor agonist TA-316 contributes to platelet biogenesis from human iPS cells. Blood Advances. 2017, 1(7), 468-76. doi: https://doi.org/10.1182/bloodadvances.2016000844.
- Nakamura S, Takayama N, Hirata S, Seo H, Endo H, Ochi K, Fujita KI, Koike T, Harimoto KI, Dohda T, Watanabe A, Okita K, Takahashi N, Sawaguchi A, Yamanaka S, Nakauchi H, Nishimura S, Eto K. Expandable Megakaryocyte Cell Lines Enable Clinically Applicable Generation of Platelets from Human Induced Pluripotent Stem Cells. Cell Stem Cell. 2014 Apr 3;14(4):535-48. (IF 22.151)
- Hirata S, Eto K. Congenital amegakaryocytic thrombocytopenia iPS cells exhibit defective MPL-mediated signaling. Journal of Clinical Investigation 123(9): 3802-14, 2013.
Stem Cell Biology and ApplicationProfessor Koji Eto
Program-specific junior associate professor Naoshi Sugimoto
Program-specific assistant professor Sou Nakamura