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Haematologica. 2013 Sep;98(9):1353-8. doi: 10.3324/haematol.2012.080424. Epub 2013 May 28.

Mouse gene targeting reveals an essential role of mTOR in hematopoietic stem cell engraftment and hematopoiesis.

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1
Department of Biotechnology, Jinan University, Guangzhou, Guangdong, China. yi.zheng@cchmc.org

Abstract

mTOR integrates signals from nutrients and growth factors to control protein synthesis, cell growth, and survival. Although mTOR has been established as a therapeutic target in hematologic malignancies, its physiological role in regulating hematopoiesis remains unclear. Here we show that conditional gene targeting of mTOR causes bone marrow failure and defects in multi-lineage hematopoiesis including myelopoiesis, erythropoiesis, thrombopoiesis, and lymphopoiesis. mTOR deficiency results in loss of quiescence of hematopoietic stem cells, leading to a transient increase but long-term exhaustion and defective engraftment of hematopoietic stem cells in lethally irradiated recipient mice. Furthermore, ablation of mTOR causes increased apoptosis in lineage-committed blood cells but not hematopoietic stem cells, indicating a differentiation stage-specific function. These results demonstrate that mTOR is essential for hematopoietic stem cell engraftment and multi-lineage hematopoiesis.

PMID:
23716557
PMCID:
PMC3762090
DOI:
10.3324/haematol.2012.080424
[Indexed for MEDLINE]
Free PMC Article
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