First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Agathe Chaigne is first author on ‘ Three-dimensional geometry controls division symmetry in stem cell colonies’, published in JCS. Agathe is a postdoc in the lab of Ewa Paluch at the MRC Laboratory for Molecular Cell Biology (LMCB), University College London, London, UK, investigating the crosstalk between cell division and cell fate transitions during development.
How would you explain the main findings of your paper in lay terms?
When an embryo develops, the cells grow and then divide to increase the size of the organism. How these cells divide, and in particular how they ensure that the two daughter cells are the same size, is important to control so that the embryo develops properly. We know many things about how cells control their orientation and daughter cell size when they grow in 2D, for example epithelial cells on a flat surface, but much less about how balls of cells such as the ones in the mouse embryo do so. Using mouse embryonic stem cells as a model system, I showed that pluripotent cells in 3D colonies divide asymmetrically in size, especially if they are situated at the periphery of the colony. I found that the connections between cells act as a stabilizer of the cell division machinery, and thus having many connections (and being in the center of the colony) pushes the cell to divide symmetrically. When cells progress towards differentiation, they change their organization from a 3D ball to a 2D sheet, and this is accompanied by a switch to more symmetric divisions.
Were there any specific challenges associated with this project? If so, how did you overcome them?
The most significant challenge, but also one of the most exciting aspects associated with the project, was the fact that mouse embryonic stem cells form 3D colonies. Therefore, I needed to perform fast 3D live imaging, which is always challenging in terms of phototoxicity. Fortunately, the LMCB has an amazing imaging facility with incredible core staff, in particular Andrew Vaughan, who helped me tremendously in setting up my spinning-disk imaging. A second part of the challenge was the analysis of 3D volumes, and this was performed using a brilliant plugin (Deforming Mesh 3D) from my co-author Matthew Smith. It is amazingly useful for extracting all sorts of features from 3D round cells (for example stem cells or cells in organoids) and it is free for all to use.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
Yes! I had two. The first was when I realized that growing the cells on an E-cadherin-coated substrate, which I took as an approach to mimic a cell growing inside a colony, made the division more symmetrical in terms of cell size! The second was when after months of trying to use immunofluorescence to detect the NuMA protein complex, I managed to find a protocol that worked great. Rocio, an amazing Spanish undergrad student from UCL, did a series of amazing experiments showing that in contrast to differentiating cells, pluripotent stem cells do not recruit NuMA at the cortex, thus explaining the lack of control in spindle position.
Why did you choose Journal of Cell Science for your paper?
I like papers from Journal of Cell Science, which are usually clear and move the field forward. I think the journal also has a strong interest in the fundamental mechanisms of cell division. I felt this was a good home for this paper, and I have been extremely satisfied with the peer review process: it was transparent, everyone was fair and courteous, and the editor was available and really understanding of work and personal circumstances, such as COVID-related lab shutdowns and maternity leave.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
I am lucky to be surrounded by amazing mentors! I get different things from each of my mentors: from Ewa Paluch, my PI, I get the expertise for all things biophysics. From Kevin Chalut, my secondary PI, I get the stem cell expertise. From Buzz Baum, whose lab I regularly invade, I get the cell division expertise. All the discussions with my peers, the PhD students and postdocs from the LMCB in general and these three labs in particular, have also made my research stronger and better.
What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?
I wanted to be a medical doctor when I was a kid, but then I decided that this was not for me. I was from a privileged enough background that I knew about research and the possibility of having a career in science, which was the closest thing. I tried it, I loved it, I stuck around. I am interested in many aspects of science, which is why I have a journalism degree and a teaching degree. I also have a degree in Chinese language and literature, but that is just because I like it!
Who are your role models in science? Why?
I am not very much into the idea of role models in science. I suppose I prefer the idea that science is done by normal people, who may be passionate about their jobs but do not need to become a role model by, for example, sacrificing their personal life or poisoning themselves with polonium. My role models are my fellow colleagues that are excited about their research, day-to-day, sometimes despite disappointing results and grant and paper rejections.
What's next for you?
I will be starting my own lab sometime in the next few months and I could not be more excited!
Tell us something interesting about yourself that wouldn't be on your CV
I play ice hockey (usually left forward, but sometimes left defender)!