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Cytokine synergies in erythropoiesis: Identifying and explaining interactions through cell division tracking and factorial design.

机译:红细胞生成中的细胞因子协同作用:通过细胞分裂跟踪和因子设计来识别和解释相互作用。

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摘要

The directed differentiation of hematopoietic cells demands fine-grained control over cell decisions. Experiments were performed to distinguish the distinct and joint effects of two cytokines---erythropoietin (EPO) and stem cell factor (SCF)---on proliferation and survival in red blood cell progenitors. An in vitro model was used to quantify these effects on erythroid progenitors. Using factorial design approach, EPO and SF were shown to have merely additive effects on cell number in two cell lines: one human erythroleukemia (TF-1), and one mouse multipotential cell line (FRCP-mix). However, a synergistic expansion of erythroid cells within differentiating FDCP-mix cultures was observed. Cell division tracking, coupled with a mathematical model of cell proliferation, quantified this response as separate sequential effects: SCF promoted early proliferation of all progenitor cells, and EPO was necessary for survival of committed erythroid progenitors. This quantitative approach suggests how separation of proliferation from death rates can identify meaningful synergism.
机译:造血细胞的定向分化需要对细胞决策的精细控制。进行实验以区分两种细胞因子-促红细胞生成素(EPO)和干细胞因子(SCF)-对红细胞祖细胞的增殖和存活的独特作用和联合作用。使用体外模型来量化这些对红系祖细胞的作用。使用阶乘设计方法,EPO和SF仅显示出对两种细胞系中细胞数量的累加效应:一种人类红白血病(TF-1)和一种小鼠多能细胞系(FRCP-mix)。但是,观察到分化的FDCP-混合培养物中红系细胞的协同扩增。细胞分裂追踪,再加上细胞增殖的数学模型,将这种反应量化为单独的顺序效应:SCF促进了所有祖细胞的早期增殖,而EPO对于定型红系祖细胞的存活是必需的。这种定量方法表明增殖与死亡率的分离如何可以确定有意义的协同作用。

著录项

  • 作者

    Horner, Daniel.;

  • 作者单位

    University of Toronto (Canada).;

  • 授予单位 University of Toronto (Canada).;
  • 学科 Biology Cell.; Engineering Biomedical.
  • 学位 M.A.Sc.
  • 年度 2006
  • 页码 110 p.
  • 总页数 110
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;生物医学工程;
  • 关键词

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