Partner: Marc Goodfellow


Recent publications
1.Phillips N., Manning C., Pettini T., Veronica B., Elli M., Peter S., Boyd J., Bagnall J., Paszek P., Spiller David G., White M., Goodfellow M., Tobias G., Magnus R., Nancy P., Stochasticity in the miR-9/Hes1 oscillatory network can account for clonal heterogeneity in the timing of differentiation, eLife, ISSN: 2050-084X, DOI: 10.7554/eLife.16118, Vol.5, pp.e16118-1-33, 2016
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.

Affiliations:
Phillips N.-other affiliation
Manning C.-other affiliation
Pettini T.-other affiliation
Veronica B.-other affiliation
Elli M.-other affiliation
Peter S.-other affiliation
Boyd J.-other affiliation
Bagnall J.-other affiliation
Paszek P.-IPPT PAN
Spiller David G.-other affiliation
White M.-other affiliation
Goodfellow M.-other affiliation
Tobias G.-other affiliation
Magnus R.-other affiliation
Nancy P.-other affiliation