Advancing Hematopoietic Stem Cell Research
through Clonal, Molecular, and Culture-Based Analysis

Our lab investigates the fundamental biology of hematopoietic stem cells (HSCs), with a particular focus on their clonal behavior, self-renewal capacity, and lineage commitment. By   prospectively   isolating   individual   mouse   HSCs   and   performing   single-cell transplantation, we demonstrated that a single cell is capable of long-term, multilineage reconstitution—work that laid the foundation for modern stem cell biology. A major ongoing effort in the lab has been to address one of the long-standing challenges in the field: robust ex vivo expansion of functional HSCs. We recently developed a chemically defined, albumin-free culture system that supports long-term expansion of mouse HSCs, and are now extending this platform to human cells. These defined conditions not only enable mechanistic studies of HSC maintenance and differentiation, but also offer a path toward safer transplantation and gene therapy without the need for toxic conditioning. We continue to refine the system and explore factors that can further improve its efficacy.
 

Representative publications:

1. Osawa   M,   Hanada   K,   Hamada   H,   Nakauchi   H   (1996).   Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science. 273(5272):242-245. PMID: 8662508

2. Ema, Hideo, et al. "Quantification of self-renewal capacity in single hematopoietic stem cells from normal and Lnk-deficient mice." Developmental cell 8.6 (2005): 907-914. PMID: 15935779

3. Yamazaki S, Ema H, Karlsson G, Yamaguchi T, Miyoshi H, Shioda S, Taketo MM, Karlsson   S,   Iwama  A,   Nakauchi   H   (2011).   Nonmyelinating   Schwann   cells maintain hematopoietic stem cell hibernation in the bone marrow niche.  Cell. 147(5):1146-1158. PMID: 22118468

4. Yamamoto, R., Morita, Y., Ooehara, J., Hamanaka, S., Onodera, M., Rudolph, K. L., ... & Nakauchi, H. (2013). Clonal analysis unveils self-renewing lineage- restricted progenitors generated directly from hematopoietic stem cells.  Cell, 154(5), 1112-1126. PMID: 23993099

5. Taya, Y., Ota, Y., Wilkinson, A. C., Kanazawa, A., Watarai, H., Kasai, M., ... & Yamazaki, S. (2016). Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation. Science, 354(6316), 1152-1155. PMID: 27934766

6. Wilkinson AC, Ishida R, Kikuchi M, Sudo K, Morita M, Crisostomo RV, Yamamoto R, Loh KM, Nakamura Y, Watanabe M, Nakauchi H*, Yamazaki S* (2019). Long- term   ex   vivo   hematopoietic   stem   cell   expansion   affords   nonconditioned transplantation. Nature. 571(7763):117-121. PMCID: PMC7006049

7. Sakurai M, Ishitsuka K, Ito R, Wilkinson AC, Kimura T, Mizutani E, Nishikii H, Sudo K, Becker HJ, Takemoto H, Sano T, Kataoka K, Takahashi S, Nakamura Y, Kent DG, Iwama A, Chiba S, Okamoto S, Nakauchi  H*, Yamazaki S*. (2023) Chemically defined cytokine-free expansion of human haematopoietic stem cells. Nature. 615:127-133. PMID:36813