Stochasticity in the miR-9/Hes1 oscillatory network can account for clonal heterogeneity in the timing of differentiation.
Elife
; 52016 10 04.
Article
em En
| MEDLINE
| ID: mdl-27700985
ABSTRACT
Recent studies suggest that cells make stochastic choices with respect to differentiation or division. However, the molecular mechanism underlying such stochasticity is unknown. We previously proposed that the timing of vertebrate neuronal differentiation is regulated by molecular oscillations of a transcriptional repressor, HES1, tuned by a post-transcriptional repressor, miR-9. Here, we computationally model the effects of intrinsic noise on the Hes1/miR-9 oscillator as a consequence of low molecular numbers of interacting species, determined experimentally. We report that increased stochasticity spreads the timing of differentiation in a population, such that initially equivalent cells differentiate over a period of time. Surprisingly, inherent stochasticity also increases the robustness of the progenitor state and lessens the impact of unequal, random distribution of molecules at cell division on the temporal spread of differentiation at the population level. This advantageous use of biological noise contrasts with the view that noise needs to be counteracted.
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MEDLINE
Assunto principal:
Células-Tronco
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Diferenciação Celular
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Regulação da Expressão Gênica
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MicroRNAs
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Proliferação de Células
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Fatores de Transcrição HES-1
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Neurônios
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article