Inferring stem cell quiescence dynamics from time-stamped single-molecule measurements – QDynamics

Adult stem cells (SCs) often “rest” in quiescence, itself a dynamic state composed of sub-states that SCs transit through. Using the neural stem cell (NSC) niche of the zebrafish adult brain, we will combine scRNAseq, single-molecule gene expression analyses and direct temporal measurement in individual NSCs in situ to identify a time-stamped transcriptional code of quiescence sub-states. We will build a probabilistic model of sub-state transitions predicting the topology and dynamics of the quiescence trajectory(ies), and validate this model by live cell tracking in vivo. Finally, we will search for the (epi)genetic regulations controlling quiescence progression through its trajectory(ies). Beyond NSCs, this project will extend the fundamental concept of sub-states to non-dividing cells, and will generate novel tools to predict cell state transition in single cells and to map single-molecule gene expression and chromatin topology in single cells in whole-mount tissues.