【摘要】 在结肠隐窝中,干细胞分化为短暂扩增细胞,短暂扩增细胞再分化为完全分化细胞.为了维持体内平衡,这2个分化概率必受到线性反馈(L)或饱和反馈(S)的调节.不同细胞可以采用不同的调节方式,产生LL、LS、SL和SS这4种耦合反馈.该文借鉴信号转导理论,引入增益因子,运用Fokker-Planck方程,推导出信号-噪声公式,并借助数值模拟,比较4种耦合反馈对信号噪声的影响.研究结果表明:相对于LL耦合反馈和LS耦合反馈,SL耦合反馈和SS耦合反馈更能合理地解释结直肠癌的"腺瘤"或"良性阶段"以及"最佳治疗"时期.因此,SL和SS耦合反馈可能是调节细胞分化的最佳耦合方式.研究结果可以为临床上正确认识结直肠癌的发展过程并制定有效的治疗方案提供理论依据.更多还原

【Abstract】 In colonic crypts, stem cells differentiate into transit-amplifying cells, and transit-amplifying cells differentiate into fully differentiated cells.In order to maintain homeostasis, the two differentiation rates must be regulated by linear feedback(L) or saturated feedback(S).Different cells can adopt different adjustment methods to generate four coupled feedbacks such as LL,LS,SL and SS.According to the signal transduction theory, a gain factor is introduced.Using the Fokker-Planck equation, the gain-noise relation is derived.Through the numerical simulation, the effects of four feedbacks on signal noise are compared.The results show that, compared with LL feedback or LS feedback, SL feedback or SS feedback can more reasonably explain the "adenoma" or "benign stage" and the "best treatment" period of colorectal cancer.Therefore, SL feedback or SS feedback may be the best coupled method to regulate cell differentiation.The above result can provide a theoretical basis for correctly understanding the development process of colorectal cancer and formulating effective treatment plans.更多还原