Pluripotent embryonic stem cells (ESCs) contain the ability to constitute the cell types of the adult vertebrate through a series of developmental state transitions. In culture, ESCs reversibly transition between states in a manner previously described as stochastic. However, whether ESCs retain memory of their previous states or transition in a memoryless (Markovian) process remains relatively unknown. Here we show lineages of ESCs do not exhibit the Markovian property: their previous states and kin relations influence future choices. In a subset of lineages, related ESCs remain likely to occupy the same state weeks after labeling. Unexpectedly, the distribution of lineages across states away from the equilibrium point predicted by a Markov model remains consistent over time, suggesting a conservation of informational entropy in this system. Additionally, some lineages appear highly dynamic in their ability to switch states but do not dominate the culture, suggesting that state switching is a separable property from growth. Together, these data suggest ESC state transitions are a proscribed process governed by additional variables.

中文翻译：

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胚胎干细胞谱系显示非马尔可夫状态转变

多能胚胎干细胞（ESC）具有通过一系列发育状态转变来构成成年脊椎动物细胞类型的能力。在文化中，ESC以先前描述的随机方式在状态之间可逆转换。但是，ESC是保留其先前状态的存储还是以无记忆（马尔可夫式）过程进行转换仍然是一个未知数。在这里，我们显示了ESC的血统并没有表现出马尔可夫性质：它们的先前状态和亲属关系会影响未来的选择。在一部分谱系中，相关的ESC在标记后几周仍可能占据相同的状态。出乎意料的是，沿马尔可夫模型预测的远离平衡点的各州之间的谱系分布随时间保持一致，这表明该系统中信息熵的守恒。另外，某些谱系在切换状态方面表现出高度的动态性，但并不能支配文化，这表明状态切换是与生长分离的特性。这些数据加在一起表明ESC状态转换是受其他变量控制的禁止过程。