Mechanical signalling in pluripotency
| Dates: | 19 January 2016 |
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| Times: | 13:00 - 14:00 |
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| What is it: | Seminar |
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| Organiser: | Faculty of Life Sciences |
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| Who is it for: | University staff, Current University students |
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| Speaker: | Dr Kevin Chalut |
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Embryonic stem (ES) cells can indefinitely self-renew in a state of naïve pluripotency, in which they are competent to generate all somatic cells. It has been hypothesized that, before irreversibly committing, ES cells pass through at least one transition state. This transition would represent a gateway for differentiation and reprogramming of somatic cells. Using a combination of specially engineered substrates, microfluidics and atomic force microscopy, we are seeking to better understand how the exit from naïve pluripotency is regulated. I will report progress on some of those results. Furthermore, I will discuss the specific role of nuclear mechanics and shape in the exit from pluripotency. Specifically, we sought a mechanical phenotype of transition by probing the nuclear response to compressive and tensile forces and found that, only during transition, nuclei of ESCs are auxetic: they displayed a cross-sectional expansion when stretched and a cross-sectional contraction when compressed, and their stiffness increased under compression1. We showed recently that the auxetic phenotype of transition ESC nuclei is driven at least in part by global chromatin decondensation. Our findings highlight the importance of nuclear structure in the regulation of differentiation and reprogramming. Importantly, there are also significant volume and shape implications we explored for the auxetic phenotype in ESC nuclei during transition. Stretched auxetic nuclei expand significantly in volume, whilst compressed auxetic nuclei condense significantly in volume; this is very unlike most materials, which tend to conserve or lose volume under stress. Therefore, I will discuss how the physical properties of these nuclei in a dynamically remodeling tissue could enhance differentiative capacity by acting as stress-driven auxetic pumps to increase molecular turnover. I will also show that changes in the tension of the actin cortex of the cells are responsible for propagating forces from the substrate to the nucleus. The forces resulting from changes in tension cause substantial changes in nuclear shape during the exit from pluripotency. Taken together, our results suggest a very important role for nuclear mechanics in regulating pluripotency.
Speaker
Dr Kevin Chalut
Organisation: Cambridge Stem Cell Institute
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Michael Smith Lecture Theatre
Michael Smith Building
Manchester
