期刊
EXPERIMENTAL HEMATOLOGY
卷 63, 期 -, 页码 12-16出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.exphem.2018.04.004
关键词
-
资金
- Japan Society for the Promotion of Science
- Japan Science and Technology Agency, Ministry of Education, Culture, Sport, Science, and Technology
- California Institute of Regenerative Medicine
- Ludwig Foundation
- National Institutes of Health National Center for Advancing Translational Science Clinical and Translational Science Award [UL1TR001085]
- Glenn Center Seed Grant
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. (C) 2018 ISEH Society for Hematology and Stem Cells. Published by Elsevier Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据