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

F Guo, S Zhang, M Grogg, JA Cancelas… - …, 2013 - ncbi.nlm.nih.gov
Haematologica, 2013ncbi.nlm.nih.gov
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 …
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.
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