2026-04-17T10:48:57Zhttps://recercat.cat/oai/request
oai:recercat.cat:2445/1724692025-12-05T09:22:47Zcom_2072_1057col_2072_478799col_2072_478917
RECERCAT author Guo, Fukun author Zhang, Shuangmin author Grogg, Matthew author Cancelas, Jose A. author Varney, Melinda E. author Starczynowski, Daniel T. author Du, Wei author Yang, Jun-Qi author Liu, Wei author Thomas, George author Kozma, Sara author Pang, Qishen author Zheng, Yi 2020-11-30T17:06:04Z2020-11-30T17:06:04Z2013-09-012020-11-30T17:06:04Z 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. (c) Ferrata Storti Foundation, 2013 info:eu-repo/semantics/openAccess Hematopoesi Fisiologia Genètica Hematopoiesis Physiology Genetics Mouse gene targeting reveals an essential role of mTOR in hematopoietic stem cell engraftment and hematopoiesis info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion