SUZUKI Takahiro The University of Tokyo, Faculty of Medicine, Visiting Research Associate, 医学部附属病院, 客員助手 (40345210)
KUMANO Keiki The University of Tokyo, Faculty of Medicine, Project Research Associate, 医学部附属病院, 特任助手 (90396721)
NAKAGAWA Masahiro The University of Tokyo, Faculty of Medicine, Medical Staff, 医学部附属病院, 医員 (10431850)
Notch signaling enables the hematopoietic stem cells (HSC) to expand ex vivo while maintaining their immaturity. It is, however, to be determined whether the Notch signaling plays an important role in the bone marrow niche for the self HSC renewal. In this project, we aimed at approaching this question by using mice variably lacking Notch1 and/or Notch2 genes or wild-type mice administered with YO01027, a Notch signaling inhibitor. First, we compared the absolute number of recovering Lin-Scal+cKit+ (LSK) cells or CD34-LSK cells in the bone marrow of Notchl+/-Notch2+/- mice after administration with 5-FU, or wild-type mice administered with 5-FU followed by the YO01027 administration. Contrary to our expectation, however, we were unable to find the difference in either kind of experiment, compared with the control mice, and thus, no proof was obtained supporting the hypothesis that Notch signaling plays a physiological role in the HSC maintenance in the bone marrow.
The successful induction of HSC from human embryonic stem (ES) cells allows us to consider various applications of those HSC, such as the industrialized production of clinical use-oriented blood cells. In this project, we investigated whether the HSC could be generated from human ES cells, based on our previous finding that Notch signaling plays an important role in HSC generation during embryogenesis. We induced differentiation from a human ES cell line, KhES-3, and sorted ES cell-derived cells using various combinations of surface markers that potentially represent HSC, such as CD34, CD133, KDR, CD90, CD150, CD105, PCLP-1, PECAM1, and VE-Cadherin. Those that were sorted as such, however, showed the potential to differentiate into endothelial cells and macrophages, but we were unable to identify the cells showing remarkable hematopoietic actiity.