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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.

Original publication

DOI

10.1126/science.aag3145

Type

Journal article

Journal

Science

Publication Date

02/12/2016

Volume

354

Pages

1152 - 1155

Keywords

Animals, Cell Proliferation, Cysteine, Diet, Female, Hematopoiesis, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, Humans, Iatrogenic Disease, Mice, Mice, Inbred C57BL, Stem Cell Niche, Valine