TY - GEN A1 - Pretschner, Anna A1 - Pabel, Sophie A1 - Haas, Markus A1 - Heiner, Monika A1 - Marwan, Wolfgang T1 - Regulatory dynamics of cell differentiation revealed by true time series from multinucleate single cells T2 - Frontiers in Genetics N2 - Dynamics of cell fate decisions are commonly investigated by inferring temporal sequences of gene expression states by assembling snapshots of individual cells where each cell is measured once. Ordering cells according to minimal differences in expression patterns and assuming that differentiation occurs by a sequence of irreversible steps, yields unidirectional, eventually branching Markov chains with a single source node. In an alternative approach, we used multi-nucleate cells to follow gene expression taking true time series. Assembling state machines, each made from single-cell trajectories, gives a network of highly structured Markov chains of states with different source and sink nodes including cycles, revealing essential information on the dynamics of regulatory events. We argue that the obtained networks depict aspects of the Waddington landscape of cell differentiation and characterize them as reachability graphs that provide the basis for the reconstruction of the underlying gene regulatory network. KW - single cell time series KW - gene regulatory network KW - Petri net KW - Markov chain KW - systems biology KW - Waddington landscape Y1 - 2021 U6 - https://doi.org/10.3389/fgene.2020.612256 SN - 1664-8021 N1 - This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). IS - 11 ER -