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Transition state dynamics during a stochastic fate choice

Antolović, V; Lenn, T; Miermont, A; Chubb, JR; (2019) Transition state dynamics during a stochastic fate choice. Development , 146 (12) , Article dev173740. 10.1242/dev.173740. Green open access

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Abstract

The generation of multiple fates from a uniform cell population via self-organisation is a recurring feature in development and regeneration. However, for most self-organising systems, we have little understanding of the processes that allow cells to become different. One of the clearest examples of developmental self-organisation is shown by Dictyostelium, with cells segregating into two major fates, stalk and spore, within multicellular aggregates. To characterise the gene expression decisions underlying this cell fate bifurcation, we carried out single cell transcriptomics on Dictyostelium aggregates. Our data show the transition of progenitors into prespore and prestalk cells occurs via distinct developmental intermediates. Few cells were captured switching between states, with minimal overlap in fate marker expression between cell types, suggesting states are discrete and transitions rapid. Surprisingly, fate-specific transcript dynamics were a small proportion of overall gene expression changes, with transcript divergence coinciding precisely with large scale remodelling of the transcriptome shared by prestalk and prespore cells. These observations suggest the stepwise separation of cell identity is temporally coupled to global expression transitions common to both fates.

Type: Article
Title: Transition state dynamics during a stochastic fate choice
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/dev.173740
Publisher version: https://doi.org/10.1242/dev.173740
Language: English
Additional information: This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: single cell transcriptomics, stochastic gene expression, symmetry-breaking, Dictyostelium, attractor state, MS2
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10071020
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