摘要：SummaryPluripotent 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.Graphical abstractDisplay OmittedHighlights•Dynamics of embryonic stem cells switching between Nanog and Sox2 defined states•Lineage-level dynamics are non-Markov over a time period of days to weeks•A subset of lineages shows high transition rate between states•These lineages skew cell fate under retinoic acid differentiationCell biology; Stem cells research; Developmental biology; Embryology; Systems and computational biology
