Standard Sub-Thermoneutral Caging Temperature Influences Radiosensitivity of Hematopoietic Stem and Progenitor Cells

摘要: The production of new blood cells relies on a hierarchical network hematopoietic stem and progenitor (HSPCs). To maintain lifelong hematopoiesis, HSPCs must be protected from ionizing radiation or other cytotoxic agents. For many years, murine models have been valuable source information regarding factors that either enhance reduce the survival after exposure marrow to radiation. In recent series studies, however, it has become clear housing-related such as cool room temperature required for laboratory mice can exert surprising influence outcome experiments. Here we report mild, but chronic cold-stress endured by housed under these conditions exerts protective effect both non-lethal lethal doses total body irradiation (TBI). Alleviation this housing at thermoneutral (30°C) resulted in significantly greater baseline radiosensitivity dose TBI with more undergoing apoptosis following TBI. Cold-stressed elevated levels norepinephrine, key molecule sympathetic nervous system binds β-adrenergic receptors. We show blocking signaling pathway vivo through use β-blocker propanolol completely mitigates HSPC apoptosis. Collectively study demonstrates stress standard increases resistance TBI-induced mechanism depends upon signaling. Since β-blockers are commonly prescribed wide variety patients, could important when predicting clinical impact sensitivity