2026-04-14T07:20:19Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1724692025-12-05T09:22:47Zcom_2072_1057col_2072_478799col_2072_478917

00925njm 22002777a 4500 dc 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 author 2020-11-30T17:06:04Z 2020-11-30T17:06:04Z 2013-09-01 2020-11-30T17:06:04Z 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. Hematopoesi Fisiologia Genètica Hematopoiesis Physiology Genetics Mouse gene targeting reveals an essential role of mTOR in hematopoietic stem cell engraftment and hematopoiesis