Background
Stem cells enable the body to maintain a pool of differentiated cells that sustain organ function. Remarkably, the number of fat cells remains largely constant throughout adult life, suggesting that stem cell engagement is finely tuned. Consistent with this, exposing adipose-derived stem and progenitor cells (ASPCs) to a differentiation cocktail triggers differentiation in only a subset of cells, while the remainder retain a non-differentiated identity. This observation is all the more striking given that all cells share the same environment and genotype prior to induction, pointing to a role for epigenetic regulation.
Aim of the project
To elucidate the epigenetic mechanisms underlying cellular heterogeneity, the student will generate human ASPCs carrying reporters for adipogenic markers using CRISPR technology (in collaboration with Kay Schink, Institute of Basic Medical Sciences). The student will then employ live-cell microscopy to visualise the dynamics of differentiation at single-cell resolution and to assess how pharmacological interventions, such as SUMOylation inhibition, affect this process.
About the group
Our group investigates the regulation of chromatin, epigenetics, and gene expression by the small ubiquitin-like modifier SUMO during cellular differentiation. Using mouse cellular systems, we have demonstrated that chromatin-bound SUMO supports transcription during adipocyte differentiation. In addition, we have shown that SUMO regulates human adipocyte identity and metabolism.
If you are interested in this project, please contact the main supervisor.
Relevant literature
Molecular mechanisms of adipogenesis: https://doi.org/10.1038/s41580-021-00357-7
Effect of SUMOylation inhibition on adipogenesis and adipocyte identity:https://academic.oup.com/nar/article/54/6/gkag232/8528805
https://academic.oup.com/nar/article/50/3/1351/6517949
https://www.nature.com/articles/s41467-025-62361-1
Fat cell turnover: https://doi.org/10.1038/nature06902
Live cell imaging of adipogenesis: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30190-6?