Yakovlev A Y, Mayer-Proschel M, Noble M
Huntsman Cancer Institute, Department of Oncological Sciences, University of Utah, Salt Lake City 84108, USA.
J Math Biol. 1998 Jul;37(1):49-60. doi: 10.1007/s002850050119.
The timing of cell differentiation can be controlled both by cellintrinsic mechanisms and by cell-extrinsic signals. Oligodendrocyte type-2 astrocyte progenitor cells are known to be the precursor cells that give rise to oligodendrocytes. When stimulated to divide by purified cortical astrocytes or by platelet-derived growth factor, these progenitor cells generate oligodendrocytes in vitro with a timing like that observed in vivo. The most widely accepted model of this process assumes a cell-intrinsic biological clock that resides in the progenitor cell. The intrinsic clock model originally proposed in 1986 remains as the dominant theoretical concept for the analysis of timed differentiation in this cell lineage. However, the results of a recent experimental study (Ibarrola et al., Developmental Biology, vol. 180, 1-21, 1996) are most consistent with the hypothesis that the propensity of a clone of dividing O-2A progenitor cells initially to generate at least one oligodendrocyte may be regulated by cell-intrinsic mechanisms, but that environmental signals regulate the extent of further oligodendrocyte generation. We propose a stochastic model of cell differentiation in culture to accommodate the most recent experimental findings. Our model is an age-dependent branching stochastic process with two types of cells. The model makes it possible to derive analytical expressions for the expected number of progenitor cells and of oligodendrocytes as functions of time. The model parameters were estimated by fitting these functions through data on the average (sample mean) number of both types of cells per colony at different time intervals from start of experiment. Using this method we provide a biologically meaningful interpretation of the observed pattern of oligodendrocyte generation in vitro and its modification in the presence of thyroid hormone.
细胞分化的时间既可以由细胞内在机制控制，也可以由细胞外在信号控制。少突胶质细胞-2型星形胶质细胞祖细胞是已知的产生少突胶质细胞的前体细胞。当受到纯化的皮质星形胶质细胞或血小板衍生生长因子刺激而分裂时，这些祖细胞在体外产生少突胶质细胞的时间与体内观察到的时间相似。关于这一过程最广泛接受的模型假定存在于祖细胞中的细胞内在生物钟。1986年最初提出的内在生物钟模型仍然是分析该细胞谱系中定时分化的主导理论概念。然而，最近一项实验研究（伊巴罗拉等人，《发育生物学》，第180卷，第1 - 21页，1996年）的结果与以下假设最为一致：正在分裂的少突胶质细胞-2型祖细胞克隆最初产生至少一个少突胶质细胞的倾向可能受细胞内在机制调节，但环境信号调节少突胶质细胞进一步产生的程度。我们提出一种培养中细胞分化的随机模型，以适应最新的实验发现。我们的模型是一个具有两种细胞类型的年龄依赖性分支随机过程。该模型使得能够推导出祖细胞和少突胶质细胞预期数量作为时间函数的解析表达式。通过将这些函数与从实验开始不同时间间隔每个集落中两种细胞的平均（样本均值）数量的数据进行拟合来估计模型参数。使用这种方法，我们对体外观察到的少突胶质细胞产生模式及其在甲状腺激素存在下的变化提供了生物学上有意义的解释。
