Quantitative single-cell live imaging links HES5 dynamics with cell-state and fate in murine neurogenesis
MetadataShow full item record
Altmetrics Handle Statistics
Altmetrics DOI Statistics
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.
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
© 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/
DescriptionFunding: V.B. and J.K. were supported by a Wellcome Trust Senior Research Fellowship to N.P. (090868/Z/09/Z)
Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.