Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation

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 mortal...

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Published in:Science (American Association for the Advancement of Science) 2016-12, Vol.354 (6316), p.1152-1155
Main Authors: Taya, Yuki, Ota, Yasunori, Wilkinson, Adam C., Kanazawa, Ayano, Watarai, Hiroshi, Kasai, Masataka, Nakauchi, Hiromitsu, Yamazaki, Satoshi
Format: Article
Language:English
Subjects:
Amino acids
Animals
Blood
Bone marrow
Cell Proliferation
Constrictions
Cysteine - deficiency
Diet
Female
Hematopoiesis - physiology
Hematopoietic Stem Cell Transplantation - adverse effects
Hematopoietic Stem Cells - physiology
Hierarchies
Humans
Iatrogenic Disease
Maintenance
Metabolism
Mice
Mice, Inbred C57BL
Stem Cell Niche - physiology
Stem cells
Transplantation
Valine
Valine - deficiency
Valine - physiology
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aag3145