Guo, FukunZhang, ShuangminGrogg, MatthewCancelas, Jose A.Varney, Melinda E.Starczynowski, Daniel T.Du, WeiYang, Jun-QiLiu, WeiThomas, GeorgeKozma, SaraPang, QishenZheng, Yi2020-11-302020-11-302013-09-010390-6078https://hdl.handle.net/2445/172469mTOR 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.6 p.application/pdfeng(c) Ferrata Storti Foundation, 2013HematopoesiFisiologiaGenèticaHematopoiesisPhysiologyGeneticsinfo:eu-repo/semantics/article6729582020-11-30info:eu-repo/semantics/openAccess23716557