Stem Cell Fate Choice: Mechanisms and Modelling Workshop
Please note, abstract and registration has now closed for this event.
In this international workshop we will bring together researchers utilizing combined experimental and mathematical modelling approaches to understand how multi potent progenitor cells choose between and commit to individual fate choices.
The sessions will consist of a mixture of invited speakers and selected abstracts, and there will be ample time for all registrants to present their work in the form of posters.
Registrants are responsible for their own accommodation requirements. There are a wide range of options to suit all budgets. Some suggestions can be found here:
The University of Bath campus is easily accessed from the Bath city centre, via bus or taxi. Further information on how to travel to Bath can be found below:
Poster and Programme
Dr James Briscoe
The Francis Crick Institute, London
Dynamical landscapes of cell fate decisions
The generation of cellular diversity during development involves differentiating cells transitioning between discrete cell states. In the 1940s, the developmental biologist Conrad Waddington introduced a landscape metaphor to describe this process. The developmental path of a cell was pictured as a ball rolling through a terrain of branching valleys with cell fate decisions represented by the branch points at which the ball decides between one of two available valleys. Progress has been made in constructing quantitative dynamical models inspired by this view of cellular differentiation. A framework based on catastrophe theory and dynamical systems methods provides the foundations for quantitative geometric models of cellular differentiation. These models can be fit to experimental data and used to make quantitative predictions about cellular differentiation. The theory indicates that cell fate decisions can be described by a small number of decision structures, such that there are only two distinct ways in which cells make a binary choice between one of two fates. The approach is broadly applicable for the quantitative analysis of differentiation dynamics and for determining principles of developmental decisions.
Professor Nancy Papalopulu
Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester
The role of gene expression oscillations in cell state transitions as revealed by live imaging and modelling
In recent years, our understanding of how cells make cell state transitions has been transformed by discovery of short-time scale protein expression oscillatory dynamics. Ultradian oscillations are exemplified by the expression of HES/Her transcription factors in neural progenitors. I will describe a quantitative and dynamic single cell live imaging approach of knocked-in reporters can be combined with mathematical modelling to analyse ultradian oscillations in vivo, during mouse and zebrafish neural development. I will show that oscillations are functionally required for cell state transitions and that noise optimization by microRNA is necessary for decoding to occur.
Professor Andrea Streit
Centre for Craniofacial & Regenerative Biology, Faculty of Dentistry, Oral and Craniofacial Sciences, Kings College London
Unravelling the gene regulatory network controlling ear identity
The vertebrate inner ear is responsible for the perception of sound and balance and its complex three-dimensional architecture is intimately linked to its function in sound and balance perception. During development the inner ear arises from a pool of progenitors that initially have the potential to contribute to all sense organs and sensory ganglia in the head. How are these precursors committed to ear identity? Combining transcriptomic and epigenomic analysis with functional experiments in the chick, we have identified the gene regulatory network that promotes ear character. At the top of the inner ear determination network lies the transcription factor Sox8, which is both necessary for ear formation and sufficient to activate the ear programme in non-ear cells. Downstream of Sox8 positive feedback loops between different transcription factors stabilise ear fate. Finally, our analysis also allows us to identify new candidates for congenital deafness including the regulatory regions that control their identity. Thus, our findings not only provide new insight into how cell fate decisions are controlled as sensory progenitor cells differentiate, but also into the potential mechanism underlying hearing loss.
Other authors: Ailin Buzzi, Alexandre Thiery, Eva Hamrud, Ramya Ranganathan
Dr Igor Adameyko
Department of Physiology and Pharmacology, Karolinska Institutet and Centre for Brain Research, Medical University of Vienna
Clonal analysis informs fate selection readouts during embryonic development
Clonal analysis at single cell level enables linking cell genealogy with the transcriptional portrait of events during embryonic development by adding a clarifying layer to the moments of fate selection. We use neural crest cells and neuromesodermal progenitors to obtain additional insights into fate selection and positional codes confounding cell fate choices based on this novel methodology.
Dr Filippo Rijli
Friedrich Miescher Institute for Biomedical Research, Basel
Making faces: genetic and epigenetic regulation of cranial neural crest cell fate
Neural crest cells, commonly recognized as transient multipotent progenitors, are often regarded as the fourth germ layer due to their ability to give rise to various structures including the craniofacial skeleton, sensory systems, autonomic nervous system, peripheral glial cells, melanocytes, and cardiac cell populations. These cells originate from the dorsal neural tube during its closure and undergo epithelial-mesenchymal transition (EMT) to detach from the neural tube and migrate into the surrounding mesenchyme towards their final destinations. The migration process of neural crest cells is influenced by a range of environmental signals, which in turn determine their ultimate fate depending on their location. Despite extensive research, the precise mechanisms governing the selection of fate and control of multipotency in neural crest cells remain incompletely understood, particularly with regard to the separation of mesenchymal skeletogenic and neuro-glial progenies. Recently, through the utilization of single-cell data, we have uncovered that competing gene expression programs play a crucial role in biasing neural crest cells towards specific fates prior to their fate selection, thereby driving them towards distinct developmental trajectories. Examining the composition of these gene expression programs may shed light on the molecular mechanisms underlying the determination of downstream fates. This inquiry holds significant importance in addressing the predominant challenge in the field, which is understanding the bias towards cranial skeletogenic neural crest.
Dr Philipp Thomas
Department of Mathematics, Imperial College London
Stochastic gene expression and cell fate decisions in lineage trees
Stochasticity in gene expression is an essential source of cell-to-cell variability (or noise) among clonal cells. The variation among cells has been suggested to play a significant role in cell fate decisions. The phenomenon has been widely studied using the Gillespie Algorithm, which implicitly assumes that cells are essentially static and neither grow nor divide. In this talk, I will discuss recent developments in modelling populations of growing and dividing cells through agent-based models. I will show how gene expression noise can be quantified in lineage trees, leading to a simple lineage interpretation of snapshot data regarding cell histories. Finally, I show that lineage structure can induce bifurcations in bistable gene regulatory networks that irreversibly select fast-growing subpopulations. Despite all the noise, our results highlight how cell fate decisions can be implemented robustly across lineage trees of growing cell populations.
Other authors: Paul Piho
Dr Meritxell Sáez Cornellana
IQS, Universitat Ramon Llull, Barcelona
Gene-free landscape models for development
Fate decisions in developing tissues involve cells transitioning between a set of discrete cell states. Geometric models, often referred to as Waddington landscapes, are an appealing way to describe differentiation dynamics and developmental decisions. We consider the differentiation of neural and mesodermal cells from pluripotent mouse embryonic stem cells exposed to different combinations and durations of signalling factors. We developed a principled statistical approach using flow cytometry data to quantify differentiating cell states. Then, using a framework based on Catastrophe Theory and approximate Bayesian computation, we constructed the corresponding dynamical landscape. The result was a quantitative model that accurately predicted the proportions of neural and mesodermal cells differentiating in response to specific signalling regimes. Taken together, the approach we describe is broadly applicable for the quantitative analysis of differentiation dynamics and for determining the logic of developmental cell fate decisions.
Other authors: James Briscoe, Robert Blassberg, Elena Camacho-Aguilar, David Rand, Eric Siggia
Professor Tatjana Sauka-Spengler
Radcliffe Department of Medicine, Medical Sciences Division, University of Oxford More details coming soon.