hematopoietic system
• common myeloid progenitors (CMPs) show less active cycling
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• granulocyte-macrophage progenitors (GMPs) show less active cycling
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• mild lymphocytosis in 8-12 week old mice
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• 22 month old mice show a reduction in the number of primitive hematopoietic cells in the bone marrow
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• 22 month old mice develop leukopenia
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• bone marrow hematopoietic stem/progenitor cells (HSPCs) show a 2-fold increase in the number of long-term hematopoietic stem/progenitor cells (LT-HSCs), but not short term HSCs (St-HSCs) or multi-potent progenitors (MPPs)
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• megakaryocyte-erythroid progenitors (MEPs) show less active cycling
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• myeloid-restricted progenitor (MyePro) cells, including common myeloid progenitors (CMPs), granulocyte-macrophage progenitor (GMP), and megakaryocyte-erythroid progenitor (MEP) cells show less active cycling
• common lymphoid progenitor (CLP) and pre-pro B cells cycle more actively and incorporate more BrdU
• myeloid-biased multi-potent progenitors (MPP3s) show restricted proliferation while lymphoid-biased multi-potent progenitors (MPP4s) show more active cycling
• LSK cells show a higher rate of protein synthesis while MyePro cells show a reduced rate of protein synthesis
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• mice show elevated apoptosis across hematopoietic lineages
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• LT-HSCs exhibit a reduction in G0 phase and a corresponding increase in S/G2/M phases of the cell cycle and enhanced bromodeoxyuridine incorporation, indicating increased cycling and proliferation
• ST-HSCs and MPPs exhibit increased cycling but to a less severe degree than LT-HSCs
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cellular
• mice exhibit reduced blood leukocyte recovery following exposure to various doses of gamma radiation
• mice show increased apoptosis in all primitive hematopoietic cell types and reduced lymphoid and myeloid colon formation in response to gamma irradiation
• pre-treatment with angiogenin (ANG) protects against radiation-induced loss of the total bone marrow number and various bone marrow cell subsets and restricts HSPC and LymPro cell cycling, prevents radiation-induced loss of MyePro cell number and promotes their proliferation, and protects against irradiation-induced apoptosis in primitive hematopoietic cells
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• LT-HSCs exhibit a reduction in G0 phase and a corresponding increase in S/G2/M phases of the cell cycle and enhanced bromodeoxyuridine incorporation, indicating increased cycling and proliferation
• ST-HSCs and MPPs exhibit increased cycling but to a less severe degree than LT-HSCs
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homeostasis/metabolism
• pretreatment with angiogenin (ANG) before gamma irradiation improves survival rate from 20% to 90%
• mice exhibit reduced survival following exposure to various doses of gamma radiation
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• serial proliferative stress with weekly 5-fluorouracil injections result in excess mortality
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• under stress conditions, progenitor response to the genotoxic agent, 5-fluorouracil is exaggerated
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immune system
• mild lymphocytosis in 8-12 week old mice
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• 22 month old mice develop leukopenia
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mortality/aging
• mice exhibit reduced survival following exposure to various doses of gamma radiation
• pretreatment with angiogenin (ANG) before gamma irradiation improves survival rate from 20% to 90%
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• serial proliferative stress with weekly 5-fluorouracil injections result in excess mortality
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