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2013-09-01

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/172469

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

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https://doi.org/10.3324/haematol.2012.080424

Resum

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.

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Hematopoesi, Fisiologia, Genètica

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Hematopoiesis, Physiology, Genetics

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Articles publicats en revistes (Ciències Fisiològiques)

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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. Mouse gene targeting reveals an essential role of mTOR in hematopoietic stem cell engraftment and hematopoiesis. _Haematologica_. 2013. Vol. 98, núm. 9, pàgs. 1353-1358. [consulta: 21 de gener de 2026]. ISSN: 0390-6078. [Disponible a: https://hdl.handle.net/2445/172469]

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