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Theory of Living Matter Group

 

4th Pub tutorial

Registration:
No registration required.

Date:
Wednesday, 21th October 2015, 6pm

Venue:
Panton Arms
43 Panton St, Cambridge CB2 1HL

Catering:

As usual, snacks are provided by TLM, drinks can be bought in the pub.


“Novel single-cell sequencing methods link transcriptional and epigenetic heterogeneity”

Heather Lee, Babraham Institute

Every cell in your body contains the same genetic information, but access to this information is restricted such that specialised cell types are generated in each organ. This is achieved by epigenetic mechanisms including DNA methylation. We have recently developed a new method for studying genome-wide DNA methylation in single cells, revealing epigenetic heterogeneity in pluripotent stem cells. By combining this technique with analysis of gene expression in the same single cell (parallel single–cell genome–wide methylome and transcriptome sequencing), we have been able to reveal associations between transcriptional and epigenetic variations, allowing us to study the complexity of epigenetic regulation at unprecedented detail. These methods hold great promise for our understanding of developmental biology and for clinical applications.

“Global oscillations in DNA methylation in primed embryonic stem cells”

Steffen Rulands, Department of Physiology, Development and Neuroscience, University of Cambridge

Mouse embryonic stem cells (mESCs) primed for differentiation exist in a state of dynamic equilibrium characterised by stochastic switching between transcriptional states. Recent advances in single-cell methods highlighted the heterogeneous and dynamic nature of DNA methylation in these cells. Combining novel single-cell sequencing methods with mathematical modelling we discovered global oscillations in mESC DNA methylation affecting most parts of the genome including distal enhancers. These oscillations are dependent on DNA methylation turnover by DNMT3 and TET enzymes. We hypothesise that oscillations in DNA methylation are associated with increased transcriptional heterogeneity, thereby contributing to lineage priming in cells poised for differentiation.