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Stochastic dynamics of cell fate decisions and the gene regulatory networks that underlie them
Cell fate decision-making is responsible for development and homeostasis, and is dysregulated in disease. Despite great promise, we are yet to harness the high-resolution cell state information that is offered by single-cell genomics data to understand cell fate decision-making as it is controlled by gene regulatory networks. We describe how we leveraged joint dynamics + genomics measurements in single cells to develop a new framework for single-cell-informed Bayesian parameter inference of Ca2+ pathway dynamics in single cells. This work reveals a mapping from transcriptional state to dynamic cell fate. But no cell is an island: cell-internal gene regulatory dynamics act in concert with external signals to control cell fate. We developed a multiscale model to study the effects of cell-cell communication on gene regulatory network dynamics controlling cell fates in hematopoiesis. Specifically, we couple cell-internal ODE models with a cell signaling model defined by a Poisson process. We discovered a profound role for cell-cell communication in controlling the fates of single cells, and show how our results resolve a controversy in the literature regarding hematopoietic stem cell differentiation. Overall, we argue for the need to consider single-cell-resolved models to understand and predict the fates of cells.
Date:
14 October 2022, 14:00
Venue:
Mathematical Institute, Woodstock Road OX2 6GG
Venue Details:
L3
Speaker:
Prof Adam MacLean (USC Dornsife College of Letters, Arts and Sciences University of Southern California)
Organising department:
Mathematical Institute
Organiser:
Sara Jolliffe (University of Oxford)
Organiser contact email address:
sara.jolliffe@maths.ox.ac.uk
Host:
Prof Ruth Baker (University of Oxford)
Part of:
Mathematical Biology and Ecology
Booking required?:
Not required
Audience:
Members of the University only
Editor:
Sara Jolliffe
