Communities matter

Image

In current circumstances, community matters more than ever. It seems that co-operation in communities of cells is also important in early development of the embryo. Group leader Professor Sally Lowell (Centre for Regenerative Medicine) recently wrote on this matter in Nature Reviews Molecular Cell Biology: 'You should always keep in touch with your friends: Community effects in biology'. Here she talks about the work of her own lab looking at how cell communities work together in early embryonic development.

Nature Reviews article

Communities matter

Our lab has a longstanding interest in community effects.  This started when our PhD student Karolina Punovuori discovered that cell-cell adhesion molecules called cadherins do more than just stick cells together. It seemed that they could in fact be helping cells to coordinate differentiation decisions with their neighbours. For example, as pluripotent cells start to express one particular cadherin, called N-Cadherin,  this adhesion molecule seems to somehow be able to make cells a bit more ‘deaf’ to certain anti-neural signals. This ‘dampening’ of anti-neural signals helps to reinforce the decision to turn into a neural cell. Because cadherins bind to each other on adjacent cells, we speculate that cells might use cadherins to spread information between neighbours in something akin to a community effect.

Punovuori K, Migueles RP, Malaguti M, et al. N-cadherin stabilises neural identity by dampening anti-neural signals. Development. 2019;146(21):dev183269. Published 2019 Nov 8. doi:10.1242/dev.183269

Image

As I discussed in the Nature Reviews article, the field is looking for new technologies to help us all to identify and study community effects. Our former postdoc Dr Guillaume Blin, who now runs his own lab at the CRM, has developed software called “NesSys” that makes it possible to identify and measure the properties of every cell in relation to all of it’s neighbours within a tissue or 3D culture. This opens up the possibility of asking questions about how the differentiation decisions of one cell relate to those of the other cells in its local community.

Blin G, Sadurska D, Portero Migueles R, Chen N, Watson JA, Lowell S. Nessys: A new set of tools for the automated detection of nuclei within intact tissues and dense 3D cultures. PLoS Biol. 2019;17(8):e3000388. Published 2019 Aug 9. doi:10.1371/journal.pbio.3000388

What next?

Looking to the future, the lab are working hard to use NesSys to explore community effects at gastrulation and during differentiation of pluripotent cells in a dish. For example, PhD student Darren Wisniewski is examining mechanisms that seem to coordinate mesoderm differentiation between nearby cells under certain conditions. Postdoc Matt Malaguti is working with PhD student Jen Annoh to develop new synthetic biology tools to give us an alternative non-imaging based approach to study how cells influence their neighbours during differentiation, and PhD student Matt French, in collaboration with CRM PI Linus Shumacher, is exploring how we can add some mathematical rigour to these ideas by modelling the effects of different types of neighbour-interactions.

So, the whole lab are working together to a common goal of understanding how local communities of cells help each other to decide their collective differentiated fate. We are delighted to have recently been awarded funding from the Wellcome Trust to keep pushing this work forward.

Image

Professor Sally Lowell is a group leader at the Centre for Regenerative Medicine and Wellcome Trust Senior Research Fellow.