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

Author

Listed:
  • Cerys S. Manning

    (The University of Manchester)

  • Veronica Biga

    (The University of Manchester)

  • James Boyd

    (University of Liverpool)

  • Jochen Kursawe

    (The University of Manchester)

  • Bodvar Ymisson

    (The University of Manchester)

  • David G. Spiller

    (The University of Manchester)

  • Christopher M. Sanderson

    (University of Liverpool)

  • Tobias Galla

    (University of Manchester)

  • Magnus Rattray

    (The University of Manchester)

  • Nancy Papalopulu

    (The University of Manchester)

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.

Suggested Citation

  • Cerys S. Manning & Veronica Biga & James Boyd & Jochen Kursawe & Bodvar Ymisson & David G. Spiller & Christopher M. Sanderson & Tobias Galla & Magnus Rattray & Nancy Papalopulu, 2019. "Quantitative single-cell live imaging links HES5 dynamics with cell-state and fate in murine neurogenesis," Nature Communications, Nature, vol. 10(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10734-8
    DOI: 10.1038/s41467-019-10734-8
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    Cited by:

    1. Fangfang Qu & Wenjia Li & Jian Xu & Ruifang Zhang & Jincan Ke & Xiaodie Ren & Xiaogao Meng & Lexin Qin & Jingna Zhang & Fangru Lu & Xin Zhou & Xi Luo & Zhen Zhang & Minhan Wang & Guangming Wu & Duanqi, 2023. "Three-dimensional molecular architecture of mouse organogenesis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Yujin Harada & Mayumi Yamada & Itaru Imayoshi & Ryoichiro Kageyama & Yutaka Suzuki & Takaaki Kuniya & Shohei Furutachi & Daichi Kawaguchi & Yukiko Gotoh, 2021. "Cell cycle arrest determines adult neural stem cell ontogeny by an embryonic Notch-nonoscillatory Hey1 module," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

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