Rostovskaya Group
Molecular control of cell fate decisions during early human development
Key words
Development, human pluripotent stem cells, differentiation, genomics, epigenetics
Research Summary
The entire human body develops from a small group of initially equivalent cells in the early embryo. How do cells decide their fate? Our lab investigates the molecular mechanisms that ensure cell fate decisions occur at the right time and in the correct order.
Cell fate specification has traditionally been understood in terms of induction, whereby cells receive instructive differentiation signals from surrounding tissues at specific locations. However, recent studies in human embryos show that differentiated lineages emerge sequentially over time, even though many of these inductive signals are continuously present throughout this dynamic process.
This apparent inconsistency reveals that, while inductive signals provide positional information and can account for the spatial organisation of cell identities, they are insufficient to explain their temporal progression alone. Additional regulatory mechanisms must therefore control the timing of cell fate decisions.
Our key question is how cells respond to instructive signals at the right time during embryonic development. To address this, we have established a human pluripotent stem cell (hPSC)-based experimental system that recapitulates the molecular dynamics and timing of early development. This highly tractable model provides a powerful platform to study human development avoiding the use of embryos.
We investigate the genetic and epigenetic mechanisms that enable cells to differentiate. We combine detailed molecular characterisation of cells undergoing developmental progression with computational modelling to reveal the underlying principles of this process. We then interrogate these mechanisms using targeted genetic and epigenetic perturbations. In the long term, we aim to reconstruct these pathways using synthetic biology approaches to uncover fundamental principles governing cell fate specification.
Join us
We offer undergraduate, MPhil, and PhD research projects, as well as opportunities to join the lab as a team member. If you are interested, please send an informal enquiry to Maria Rostovskaya outlining your research interests and attaching your CV.
Selected publications
1. Coussement L, Ciarchi M, Kolmogorova A, De Meyer T, Rulands S, Reik W, Rostovskaya M. A transcriptional clock of the human pluripotency transition. Biorxiv. DOI: 10.1101/2025.03.13.643129. In revision. (Lead author)
2. Nocente MC, Della Rosa M, Malcolm AA, Lister G, Savin I, Ray-Jones H, Elderkin S, Tian R, Andrews S, Bendall A, Semprich CI, Kampman M, Malysheva V, Rostovskaya M*, Rugg-Gunn PJ*, Spivakov M*. Poising and connectivity of emergent human developmental enhancers in the transition from naive to primed pluripotency. Biorxiv. DOI: 10.1101/2025.10.02.679816. Accepted at Cell Reports. (*co-senior and co-corresponding authors)
3. de Sousa JA, Wong C-W, Dunkel I, Owens T, Voigt P, Hodgson A, Baker D, Schulz E, Reik W, Smith A, Rostovskaya M*, von Meyenn F*. Epigenetic dynamics during capacitation of naïve human pluripotent stem cells. Science Adv. 2023; 9(39): eadg1936. PMID:37774033. DOI: 10.1126/sciadv.adg1936 (*co-senior and co-corresponding authors)
4. Rostovskaya M*, Andrews S, Reik W*, Rugg-Gunn PJ*. Amniogenesis occurs in two independent waves in primates. Cell Stem Cell. 2022; 29(5): 744-759. PMID:35439430. DOI: 10.1016/j.stem.2022.03.014 (*co-corresponding authors)
5. Rostovskaya M. Capacitation of human naïve pluripotent stem cells. Methods in Mol. Biol. 2022; Vol. 2416, Chapter 9. PMID: 34870834. DOI: 10.1007/978-1-0716-1908-7_9
6. Rostovskaya M*, Stirparo G, Smith A*. Capacitation of human naïve pluripotent stem cells for multi-lineage differentiation. Development. 2019; 146: 1-15. PMID:30944104. DOI: 10.1242/dev.172916 (*co-corresponding authors)
7. Rostovskaya M*, Donsanthe S, Sacchetti B, Alexopoulou D, Klemroth S, Dahl A, Riminucci M, Bianco P, Anastassiadis K*. Clonal analysis delineates transcriptional programs of osteogenic and adipogenic lineages of adult mouse skeletal progenitors. Stem Cell Reports. 2018; 11(1): 212-227. PMID:29937146. DOI: 10.1016/j.stemcr.2018.05.014 (*co-corresponding authors)
8. Rostovskaya M, Fu J, Obst M, Baer I, Weidlich S, Wang H, Smith AJ, Anastassiadis K, Stewart AF. Transposon-mediated BAC transgenesis in human ES cells. Nucleic Acids Res. 2012; 40(19): e150. PMID:22753106. DOI: 10.1093/nar/gks643
Contact details
Group Leader:
Dr Maria Rostovskaya
Address:
The Gurdon Institute,
Henry Wellcome Building of Cancer and Developmental Biology,
Tennis Court Road,
Cambridge,
CB2 1QN,
UK
Email: mr631 at cam.ac.uk