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Quantitative single-cell live imaging links HES5 dynamics with cell-state and fate in murine neurogenesis

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Manning_2019_Quantitative_single_NComms_2835.pdf (3.750Mb)
Date
27/06/2019
Author
Manning, Cerys S.
Biga, Veronica
Boyd, James
Kursawe, Jochen
Ymisson, Bodvar
Spiller, David G.
Sanderson, Christopher M.
Galla, Tobias
Rattray, Magnus
Papalopulu, Nancy
Keywords
QA Mathematics
QH301 Biology
DAS
BDC
R2C
Metadata
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Abstract
During embryogenesis cells make fate decisions within complex tissue environments. The levels and dynamics of transcription factor expression regulate these decisions. Here, we use single cell live imaging of an endogenous HES5 reporter and absolute protein quantification to gain a dynamic view of neurogenesis in the embryonic mammalian spinal cord. We report that dividing neural progenitors show both aperiodic and periodic HES5 protein fluctuations. Mathematical modelling suggests that in progenitor cells the HES5 oscillator operates close to its bifurcation boundary where stochastic conversions between dynamics are possible. HES5 expression becomes more frequently periodic as cells transition to differentiation which, coupled with an overall decline in HES5 expression, creates a transient period of oscillations with higher fold expression change. This increases the decoding capacity of HES5 oscillations and correlates with interneuron versus motor neuron cell fate. Thus, HES5 undergoes complex changes in gene expression dynamics as cells differentiate.
Citation
Manning , C S , Biga , V , Boyd , J , Kursawe , J , Ymisson , B , Spiller , D G , Sanderson , C M , Galla , T , Rattray , M & Papalopulu , N 2019 , ' Quantitative single-cell live imaging links HES5 dynamics with cell-state and fate in murine neurogenesis ' , Nature Communications , vol. 10 , 2835 . https://doi.org/10.1038/s41467-019-10734-8
Publication
Nature Communications
Status
Peer reviewed
DOI
https://doi.org/10.1038/s41467-019-10734-8
ISSN
2041-1723
Type
Journal article
Rights
© The Author(s) 2019. This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made. The images or other third partymaterial in this article are included in the article’s Creative Commons license, unlessindicated otherwise in a credit line to the material. If material is not included in thearticle’s Creative Commons license and your intended use is not permitted by statutoryregulation or exceeds the permitted use, you will need to obtain permission directly fromthe copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/
Description
Funding: V.B. and J.K. were supported by a Wellcome Trust Senior Research Fellowship to N.P. (090868/Z/09/Z)
Collections
  • University of St Andrews Research
URI
http://hdl.handle.net/10023/18276

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