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dc.contributor.authorSoto, Ximena
dc.contributor.authorBiga, Veronica
dc.contributor.authorKursawe, Jochen
dc.contributor.authorLea, Robert
dc.contributor.authorDoostdar, Parnian
dc.contributor.authorThomas, Riba
dc.contributor.authorPapalopulu, Nancy
dc.identifier.citationSoto , X , Biga , V , Kursawe , J , Lea , R , Doostdar , P , Thomas , R & Papalopulu , N 2020 , ' Dynamic properties of noise and Her6 levels are optimized by miR-9, allowing the decoding of the Her6 oscillator ' , EMBO Journal , vol. 39 , no. 12 , e103558 .
dc.identifier.otherRIS: urn:1F48B7FC5DA7D320B39B903602918EAC
dc.identifier.otherORCID: /0000-0002-0314-9623/work/74118152
dc.descriptionThis work was supported by a Wellcome Trust Senior Research Fellowship to NP (106185/Z/14/Z).en
dc.description.abstractNoise is prevalent in biology and has been widely quantified using snapshot measurements. This static view obscures our understanding of dynamic noise properties and how these affect gene expression and cell state transitions. Using a CRISPR/Cas9 Zebrafish her6::Venus reporter combined with mathematical and in vivo experimentation, we explore how noise affects the protein dynamics of Her6, a basic helix‐loop‐helix transcriptional repressor. During neurogenesis, Her6 expression transitions from fluctuating to oscillatory at single‐cell level. We identify that absence of miR‐9 input generates high‐frequency noise in Her6 traces, inhibits the transition to oscillatory protein expression and prevents the downregulation of Her6. Together, these impair the upregulation of downstream targets and cells accumulate in a normally transitory state where progenitor and early differentiation markers are co‐expressed. Computational modelling and double smFISH of her6 and the early neurogenesis marker, elavl3, suggest that the change in Her6 dynamics precedes the downregulation in Her6 levels. This sheds light onto the order of events at the moment of cell state transition and how this is influenced by the dynamic properties of noise. Our results suggest that Her/Hes oscillations, facilitated by dynamic noise optimization by miR‐9, endow progenitor cells with the ability to make a cell state transition.
dc.relation.ispartofEMBO Journalen
dc.subjectCell state transitionsen
dc.subjectGene expression noiseen
dc.subjectHer6 oscillationsen
dc.subjectZebrafish neurogenesisen
dc.subjectQH301 Biologyen
dc.titleDynamic properties of noise and Her6 levels are optimized by miR-9, allowing the decoding of the Her6 oscillatoren
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews. Applied Mathematicsen
dc.description.statusPeer revieweden

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