Udomlumleart Tee, Hu Sofia, Garg Salil
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
iScience. 2021 Jul 17;24(8):102879. doi: 10.1016/j.isci.2021.102879. eCollection 2021 Aug 20.
Pluripotent embryonic stem cells (ESCs) constitute the cell types of the adult vertebrate through a series of developmental state transitions. These states can be defined by expression levels of marker genes, such as Nanog and Sox2. In culture, ESCs reversibly transition between states. However, whether ESCs retain memory of their previous states or transition in a memoryless (Markovian) process remains relatively unknown. Here, we show some highly dynamic lineages of ESCs do not exhibit the Markovian property: their previous states and kin relations influence future choices. Unexpectedly, the distribution of lineages across their composition between states is constant over time, contrasting with the predictions of a Markov model. Additionally, highly dynamic ESC lineages show skewed cell fate distributions after retinoic acid differentiation. Together, these data suggest ESC lineage is an important variable governing future cell states, with implications for stem cell function and development.
多能胚胎干细胞（ESCs）通过一系列发育状态转变构成成年脊椎动物的细胞类型。这些状态可以由标记基因（如Nanog和Sox2）的表达水平来定义。在培养中，ESCs在不同状态之间可逆地转变。然而，ESCs是保留其先前状态的记忆还是以无记忆（马尔可夫）过程进行转变，仍然相对未知。在这里，我们表明一些高度动态的ESCs谱系不具有马尔可夫特性：它们先前的状态和亲属关系会影响未来的选择。出乎意料的是，随着时间的推移，谱系在不同状态之间的组成分布是恒定的，这与马尔可夫模型的预测形成对比。此外，高度动态的ESCs谱系在视黄酸分化后显示出细胞命运分布的偏态。总之，这些数据表明ESCs谱系是控制未来细胞状态的一个重要变量，对干细胞功能和发育具有重要意义。
