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

作者：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^*

来源：Haematologica-The Hematology Journal, 2013, 98(9): 1353-1358.

DOI：10.3324/haematol.2012.080424

• MAMMALIAN TARGET
• SELF-RENEWAL
• LEUKEMIA
• PTEN
• DIFFERENTIATION
• QUIESCENCE
• RICTOR

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.

• 出版日期2013-9
• 单位暨南大学