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Mouse gene targeting reveals an essential role of mTOR in hematopoietic stem cell engraftment and hematopoiesis Guo, Fukun Zhang, Shuangmin Grogg, Matthew Cancelas, Jose A. Varney, Melinda E. Starczynowski, Daniel T. Du, Wei Yang, Jun-Qi Liu, Wei Thomas, George Kozma, Sara Pang, Qishen Zheng, Yi Hematopoesi Fisiologia Genètica Hematopoiesis Physiology Genetics 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. 2020-11-30T17:06:04Z 2020-11-30T17:06:04Z 2013-09-01 2020-11-30T17:06:04Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 0390-6078 https://hdl.handle.net/2445/172469 672958 23716557 eng Reproducció del document publicat a: https://doi.org/10.3324/haematol.2012.080424 Haematologica, 2013, vol. 98, num. 9, p. 1353-1358 https://doi.org/10.3324/haematol.2012.080424 (c) Ferrata Storti Foundation, 2013 info:eu-repo/semantics/openAccess 6 p. application/pdf Ferrata Storti Foundation Articles publicats en revistes (Ciències Fisiològiques)