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Title: Mouse gene targeting reveals an essential role of mTOR in hematopoietic stem cell engraftment and hematopoiesis
Author: 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
Keywords: Hematopoesi
Issue Date: 1-Sep-2013
Publisher: Ferrata Storti Foundation
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.
Note: Reproducció del document publicat a:
It is part of: Haematologica, 2013, vol. 98, num. 9, p. 1353-1358
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ISSN: 0390-6078
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)

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