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PreprintCited by 76Neurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene RegulationGene Regulatory Network Analysis

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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, Cerys S, Biga, Veronica, Boyd, James, Kursawe, Jochen, Ymisson, Bodvar, Spiller, David G, Sanderson, Christopher M, Galla, Tobias, Rattray, Magnus, Papalopulu, Nancy·2018·Nature Communications
DOI 10.1101/373407PMC PMC6597611

Preprint — published as 10.1038/s41467-019-10734-8

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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.

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Metadata

Authors
Manning, C. S., Biga, V., Boyd, J., Kursawe, J., Ymisson, B., Spiller, D. G., Sanderson, C. M., Galla, T., Rattray, M., & Papalopulu, N.
Affiliations
  • University of Manchester (GB)
  • University of Liverpool (GB)
Corresponding author
Papalopulu, Nancy
ORCID
Venue
Nature Communications
Publisher
openRxiv
Published
2018-07-20
Volume
10
Issue
1
Pages
2835-2835
ISSN
2041-1723 (ISSN-L)
DOI
10.1101/373407
PMC
PMC6597611
OpenAlex
W2953443559
Cited by
76
References
1
Citations by year
2026: 11 · 2025: 10 · 2024: 10 · 2023: 8 · 2022: 11 · 2021: 16 · 2020: 7 · 2019: 3
FWCI
4.13
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion, other-oa)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • St Andrews Research Repository (St Andrews Research Repository) (submittedVersion, cc-by)
Funders
  • Wellcome Trust (204832/Z/16/Z, 103986, 204832/B/16/Z, 090868, 090868/Z/09/Z, 103986/Z/14/Z, 204832)
  • University of Manchester
  • Medical Research Council (MR/K015885/1, MR/M008908/1)
  • Biotechnology and Biological Sciences Research Council (BB/F005938/2, BB/K003097/1)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
Keywords
Hes5, neurogenesis, neural progenitor cells, cell fate determination, stochastic gene expression, bifurcation, mathematical modeling, interneuron differentiation, motor neuron differentiation, spinal cord development, single-cell live imaging
MeSH terms
Animals, Female, Male, Mice, Inbred ICR, Repressor Proteins, Mice, Knockout, Gene Expression Regulation, Developmental, Mice, Basic Helix-Loop-Helix Proteins, Neurogenesis, Neural Stem Cells, Single-Cell Analysis

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