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Cell Cycle Heterogeneity Can Generate Robust Cell Type Proportioning

Gruenheit, N; Parkinson, K; Brimson, CA; Kuwana, S; Johnson, EJ; Nagayama, K; Llewellyn, J; ... Thompson, CRL; + view all (2018) Cell Cycle Heterogeneity Can Generate Robust Cell Type Proportioning. Developmental Cell , 47 (4) pp. 494-508. 10.1016/j.devcel.2018.09.023. Green open access

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Abstract

Cell-cell heterogeneity can facilitate lineage choice during embryonic development because it primes cells to respond to differentiation cues. However, remarkably little is known about the origin of heterogeneity or whether intrinsic and extrinsic variation can be controlled to generate reproducible cell type proportioning seen in vivo. Here, we use experimentation and modeling in D. discoideum to demonstrate that population-level cell cycle heterogeneity can be optimized to generate robust cell fate proportioning. First, cell cycle position is quantitatively linked to responsiveness to differentiation-inducing signals. Second, intrinsic variation in cell cycle length ensures cells are randomly distributed throughout the cell cycle at the onset of multicellular development. Finally, extrinsic perturbation of optimal cell cycle heterogeneity is buffered by compensatory changes in global signal responsiveness. These studies thus illustrate key regulatory principles underlying cell-cell heterogeneity optimization and the generation of robust and reproducible fate choice in development.

Type: Article
Title: Cell Cycle Heterogeneity Can Generate Robust Cell Type Proportioning
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.devcel.2018.09.023
Publisher version: https://doi.org/10.1016/j.devcel.2018.09.023
Language: English
Additional information: © 2018 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Keywords: heterogeneity, cell cycle, single-cell sequencing, cell fate, lineage priming, Dictyostelium, oscillator
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 > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/10063462
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