title: Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation.
abstract: A specialized bone marrow microenvironment (niche) regulates hematopoietic stem cell (HSC) self-renewal and commitment. For successful donor-HSC engraftment, the niche must be emptied via myeloablative irradiation or chemotherapy. However, myeloablation can cause severe complications and even mortality. Here we report that the essential amino acid valine is indispensable for the proliferation and maintenance of HSCs. Both mouse and human HSCs failed to proliferate when cultured in valine-depleted conditions. In mice fed a valine-restricted diet, HSC frequency fell dramatically within 1 week. Furthermore, dietary valine restriction emptied the mouse bone marrow niche and afforded donor-HSC engraftment without chemoirradiative myeloablation. These findings indicate a critical role for valine in HSC maintenance and suggest that dietary valine restriction may reduce iatrogenic complications in HSC transplantation.
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Taya
authors.affiliation: Department of Pathology, Research Hospital, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Ota
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Lorry I. Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305-5461, USA.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Wilkinson
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Ayano
authors.initials: A
authors.lastname: Kanazawa
authors.affiliation: Division of Stem Cell Cellomics, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.|Impulsing Paradigm Change through Disruptive Technologies Program (ImPACT), Japan Science and Technology Agency (JST), Tokyo 102-0076, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watarai
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Kasai
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan. y-sato4@ims.u-tokyo.ac.jp nakauchi@stanford.edu.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Lorry I. Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305-5461, USA.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan. y-sato4@ims.u-tokyo.ac.jp nakauchi@stanford.edu.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamazaki
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003545:Cysteine / Q000172:deficiency; D004032:Diet; D005260:Female; D006410:Hematopoiesis / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007049:Iatrogenic Disease; D051379:Mice; D008810:Mice, Inbred C57BL; D055153:Stem Cell Niche / Q000502:physiology*; D014633:Valine / Q000172:deficiency* / Q000502:physiology
chemical_list: D014633:Valine; D003545:Cysteine