Analysis Tools
hematopoietic system
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• mice exhibit normal myeloid, T-lineage, and B-lineage distributions in the bone marrow and spleen
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• after 2 injections of 5-FU, mice exhibit a significant increase in total bone marrow cells with progenitor cell numbers higher than those in similarly treated wild-type controls
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• platelet number is significantly increased at 8-12 weeks of age
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• flow cytometry revealed a significantly higher frequency of long-term hematopoietic stem cells (LT-HSCs, defined as the CD34-Flk2-CD150+ LSK population) relative wild-type controls while total bone marrow cell count remains normal
• analysis of competitive limiting dilution bone marrow transplantation (BMT) results revealed increased numbers of functional HSCs, with mutant bone marrow cells giving rise to greater donor chimerism in all blood lineages in the recipient mice than wild-type cells
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• after a single dose of 5-Fluorouracil (5-FU), mice show a faster recovery of platelet count than wild-type controls
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• purified HSCs exhibit enhanced repopulating ability and self-renewal upon serial transplantation
• HSCs show enhanced regenerative potential following 5-FU-induced cytotoxic stress
• HSCs show decelerated cell cycle progression, increased quiescence, and downregulation of gene expression associated with cell division
• hematopoietic stem/progenitor cells (HSPCs) show enhanced signaling in response to thrombopoietin
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• at day 7 after a single 5-FU injection, HSCs regenerate faster than wild-type HSCs with increased cell proliferation, as shown by BrdU incorporation analysis
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homeostasis/metabolism
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• after a single dose of 5-Fluorouracil (5-FU), mice show a faster recovery of platelet count than wild-type controls
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• following 5-Fluorouracil (5-FU)-induced cytotoxic stress, mice exhibit faster platelet recovery after a single dose of 5-FU and increased survival upon repetitive 5-FU administration relative to similarly treated wild-type controls
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cellular
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• BrdU incorporation analysis in SLAM LSK cells revealed that HSCs exhibit a larger G0 population than wild-type HSCs, suggesting decelerated cell cycle progression
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• at day 7 after a single 5-FU injection, HSCs regenerate faster than wild-type HSCs with increased cell proliferation, as shown by BrdU incorporation analysis
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mortality/aging
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• following 5-Fluorouracil (5-FU)-induced cytotoxic stress, mice exhibit faster platelet recovery after a single dose of 5-FU and increased survival upon repetitive 5-FU administration relative to similarly treated wild-type controls
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