First Person is a series of interviews with the first authors of a selection of papers published in Biology Open, helping researchers promote themselves alongside their papers. Sophie Kraunsoe is first author on ‘ Requirement for STAT3 and its target, TFCP2L1, in self-renewal of naïve pluripotent stem cells in vivo and in vitro’, published in BiO. Sophie conducted the research described in this article while an MPhil student in Jenny Nichols's lab at Cambridge Stem Cell Institute. She is now a PhD student in the lab of Margarida Cardoso-Moreira at the Francis Crick Institute, investigating developmental processes and how these diverge between species to drive phenotypic diversity.
Describe your scientific journey and your current research focus
I did my undergraduate degree in Natural Sciences at the University of Cambridge, thinking I wanted to become a biochemist. However, after 2 years of doing a little bit of everything, I decided to focus on developmental biology after being mesmerised by the beautiful, complex self-organisation and patterning of the embryo. My final year project was in Dr Elia Benito-Gutiérrez's lab in the Department of Zoology, studying the regulation of neuromesodermal progenitor cells in the amphioxus. Here, I was lucky enough to be mentored be a fantastic PhD student (now a post-doc), Toby Andrews, who taught me to love imaging techniques and especially to be imaginative in how to visualise data. From there, I moved to the Cambridge Stem Cell Institute to do an MPhil with Professor Jenny Nichols working with an in vitro system of human embryo implantation. In Jenny's lab, I learned new embryology and tissue culture skills with a lot of input and support from two amazing post-docs, Takuya Azami and Elena Corujo-Simon. I then moved to Professor Ramiro Alberio's lab at the University of Nottingham to continue my interest in in vitro developmental systems using pig gastruloids to model endoderm specification at gastrulation. This was a fantastic experience working with two post-docs, Andrew Strange and Luke Simpson, and our fab lab manager, Doris Klisch, to understand more about gastrulation in a bilaminar disc embryo. Recently, I started my PhD at the Francis Crick Institute in Dr Margarida Cardoso-Moreira's lab, working on the evolution of the placenta in different vertebrate species.
Who or what inspired you to become a scientist?
At high school, I always loved science and being able to explain the awesome biology in the world around me. I think I was particularly drawn to the idea that there will always be more questions in science and that our knowledge will always be incomplete. I had some very good teachers (especially Mr Bottrill and Dr Nield) who nurtured my interested and convinced me to apply for an internship at Manchester University whilst doing my A-levels. This time in the lab opened my eyes to the exciting possibilities of a career in science.
“We discovered that STAT3 and TFCP2L1 […] are required for embryonic diapause because embryos with the encoding genes knocked out lose the epiblast and primitive endoderm lineage and fail to develop.”
How would you explain the main finding of your paper?
In mice and some other species, whilst a mother is suckling a large, new litter of pups, any new embryos that are conceived arrest at an early stage of development and only resume development once the previous litter has weaned. This phenomenon is called diapause. The embryonic arrest occurs because oestrogen secretion by the mother's ovaries is suppressed when suckling a large litter. Diapause happens naturally but can also be induced artificially by removing the ovaries of the mother (ovariectomy) before the surge of oestrogen is produced just prior to implantation. Under these conditions, diapaused embryos can survive for up to a month. A cell signalling pathway called LIF signalling was known to be critical for the embryo to survive diapause. Embryos arrest at 4.5 days after fertilisation when the embryo has three lineages – the extra-embryonic trophoblast lineage, which will form the placenta, the extra-embryonic primitive endoderm lineage, which will form the yolk sac, and the embryonic lineage, the epiblast. We discovered that STAT3 and TFCP2L1 (two proteins downstream of the LIF signalling cascade) are required for embryonic diapause because embryos with the encoding genes knocked out lose the epiblast and primitive endoderm lineage and fail to develop. During diapause, epiblast cells self-renew (divide to form two new epiblast cells), and this is thought to be why mouse stem cells were so easy to derive from the embryo. Interestingly, stem cells can be derived from embryos with STAT3 knocked out but not from embryos with TFCP2L1 knocked out, suggesting that the requirements for stem cells to self-renew (divide to form two new stem cells rather than differentiating) in a dish are different to the requirement for self-renewal in the embryo.
What are the potential implications of this finding for your field of research?
The finding that the requirements for maintenance of naïve pluripotency are different in vitro compared to in vivo raises important questions and demonstrates that knocking out genes in vitro in stem cell lines and assessing the phenotype may not completely reflect the role of these factors in the embryo.
Which part of this research project was the most rewarding?
This paper has been brewing in Jenny's lab for many years and so it's fantastic to finally see it published. For me as an experimentalist, the most rewarding part of this research has been branching out and learning new computational biology skills to write the pipeline to analyse the immunofluorescence images. This was especially useful and a fun project during lockdown when access to the lab was more limited.
What do you enjoy most about being an early-career researcher?
I have been lucky enough to move between lots of different labs over the past few years, and I love being able to work with new people and live and make friends in different cities. I think being able to move between labs early in my career has helped me to build up a network and provided the opportunity to learn many different skills.
“Choosing a lab environment where you will be able to flourish professionally and personally is as important as choosing a lab that meets your research goals.”
What piece of advice would you give to the next generation of researchers?
Choosing a lab environment where you will be able to flourish professionally and personally is as important as choosing a lab that meets your research goals.
What's next for you?
This past autumn, I started my PhD at the Francis Crick Institute in the Cardoso-Moreira lab, where I will be based for the next 4 years. The lab is interested in evolutionary innovation and how complex traits evolve. To study this, we use the placenta as a model system because it has evolved independently many times across vertebrates and because the placenta is an extraordinarily diverse organ taking many different morphological forms. My project is focused on a family of placental fishes in which the placenta has evolved nine times! I want to understand how a placenta can be built from scratch over a very short evolutionary timeframe and whether convergent gains of the placenta involve co-option of the same cell types and mechanisms or divergent solutions.
Sophie Kraunsoe’s contact details: Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.