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Hematopoietic stem cells (HSCs) are used clinically in bone marrow (BM) transplantation due to their unique ability to reform the entire hematopoietic system. Recently, we reported that HSCs are highly sensitive to valine, one of the three branched-chain amino acids (BCAAs) in addition to isoleucine and leucine. Dietary depletion of valine could even be used as a conditioning regimen for HSC transplantation. Here, we report that HSCs are highly sensitive to the balance of BCAAs, with both proliferation and survival reduced by BCAA imbalance. However, low but balanced BCAA levels failed to rescue HSC maintenance. Importantly, in vivo depletion of all three BCAAs was significantly less toxic than depletion of valine only. We demonstrate that BCAA depletion can replace valine depletion as a safer alternative to BM conditioning. In summary, by determining HSC metabolic requirements, we can improve metabolic approaches to BM conditioning.

Original publication

DOI

10.1016/j.exphem.2018.04.004

Type

Journal article

Journal

Exp Hematol

Publication Date

07/2018

Volume

63

Pages

12 - 16.e1

Keywords

Anemia, Animals, Bone Marrow, Cell Survival, Cells, Cultured, Culture Media, Diet, Erythrocyte Count, Fetal Blood, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, Humans, Isoleucine, Leucine, Mice, Mice, Inbred C57BL, Radiation Chimera, Transplantation Conditioning, Valine