“The 87th of Stem Cell Biology and Regenerative Medicine Forum”
Date：Feb 8th (Mon) 2016
Time : 13:00 〜 14:30
Place：Auditorium in 1st Building------------------------------------------------------------------------------------------------------------------------------------（Internal Speaker）
13:00-13:30 Yuki Taya (Division of Stem Cell Therapy The Institute of Medical Science
The University of Tokyo)
Valine starving permits hematopoietic stem cell transplantation without
chemoirradiative myeloablation（External Speaker）
13:30-14:30 Kazuhito Naka (Department of Stem Cell Biology, Research Institute for
Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan)
A Nutrient Supply Essential for CML Stem Cells-------------------------------------------------------------------------------------------------------------------------------------

Hosted by Center for Stem Cell Biology and Regenerative Medicine---Information--＊ Please register attendance at the reception desk.
＊ Next forum（the88th）will be held on Feb 22nd.
＊ Please contact tatsu-m@ims.u-tokyo.ac.jp, for Forum speaker recommendations

Valine starving permits hematopoietic stem cell transplantation without
chemoirradiative myeloablation
Yuki Taya (Division of Stem Cell Therapy The Institute of Medical ScienceThe
University of Tokyo)

Hematopoietic stem cells (HSCs) have the potential to provide the entire range ofblood cells throughout the lifespan, maintaining the hibernation state in specializedbone marrow (BM) microenvironment called niches. Although various types ofcells and proteinous factors have been proposed to control hematopoiesis, little isknown about environmental factors crucial for the maintenance, survival andfunction of HSCs in vivo. Here we found that endogenous small molecules such asamino acids are differentially distributed to bone tissues in mice. Functional
analysis of various amino acids revealed that self-renewal of HSCs is lost under invitro culture conditions without some amino acids especially valine. Consistentwith these in vitro data, the mice fed a diet deficient in valine exhibited a massive
decrease in the frequency of BM HSCs. Furthermore, dietary deficiency of valine
could vacate BM niches and promote engraftment of donor HSCs. These findings
indicate a critical role for valine metabolism in the maintenance of HSCs and raise
the possibility that in vivo reduction of valine may become third conditioning
method for HSC transplantation.

A Nutrient Supply Essential for CML Stem Cells
Kazuhito Naka (Department of Stem Cell Biology, Research Institute forRadiation Biology and Medicine, Hiroshima University, Hiroshima, Japan)

A nutrient supply specific to the rare chronic myelogenous leukemia (CML) stem
cell population could provide a target for novel therapeutics aimed at eradicatingthese cells. In this study, we surveyed global metabolic differences between murine
normal hematopoietic stem cells (HSCs) and CML stem cells using sophisticatedmetabolomics techniques. Strikingly, we found that CML stem cells took up
significantly higher levels of dipeptide species than normal HSCs. Onceinternalized, these dipeptide species activated nutrient signaling via a pathway
involving p38MAPK and the stemness transcription factor Smad3, which promotes
CML stem cell maintenance. Importantly, pharmacological inhibition of dipeptide
uptake inhibited CML stem cell activity in vivo. Collectively, our results
demonstrated that dipeptide species support CML stem cell maintenance byguaranteeing an essential nutrient supply in vivo, and thus point towards a potential
novel therapeutic target for CML treatment.