Research Interests:
Our lab is interested in the mechanisms and biological roles of epigenetic reprogramming for pluripotency and germ cell/oocyte development. We specifically study the processes of X-chromosome in- and reactivation, classical models of epigenetics, by developing tailored mouse and human iPSC-reprogramming and organoid systems of germ cell and oocyte development. We thereby made fundamental discoveries on the interplay between 3D-genome structure, epigenetics and transcription and the importance of X-chromosome remodeling for meiosis and oogenesis. Furthermore, together with the clinic, we studied the impact of aging on the human oocyte transcriptome by single-cell RNA-Seq and derived patient-specific iPSC-lines and tested their capacity for germ cell differentiation in vitro. Our future goal is to further advance our knowledge on epigenetic changes during iPSC-reprogramming and germ cell development in vitro and thereby contribute to the development of next generation stem cell-based approaches for regenerative and reproductive medicine.
Description of the research project
We have multiple research projects available along the following main research lines:
- Epigenetic reprogramming and pluripotency:
In our previous work we identified through functional shRNA and CRISPR screens key regulators of X-chromosome reactivation and iPSC reprogramming. For example, we found cohesin to be important to change the 3D-chromatin structure when turning the X-chromosome form an OFF- to an ON-state. Furthermore, we found that inflammatory signaling pathways such as Interferon-gamma (IFNγ) boost X-chromosome reactivation and pluripotency acquisition. Future projects will involve testing if these mechanisms are conserved in other contexts of epigenetic reprogramming in vitro and in vivo, or if different regulators are at play. Furthermore, it remains to be tested, what is the mechanism of action of the other pathways, which we have identified in our genome-wide CRISPR-screen. The prospective student would learn to apply methods such as iPSC-reprogramming, CRISPR engineering of stem cells and single-cell RNA-Seq and epigenomic profiling.
- Epigenetic reprogramming and in vitro germ cell development:
Our previous work has shown the importance of X-chromosome dosage control for in vitro oogenesis from embryonic stem cells using ovarian organoids. We have thereby identified molecular pathways, which are linked with the X-chromosome state, and which affect the different steps of in vitro germ cell differentiation. The student will use CRISPR engineering to perturb these pathways and test their mechanism for oocyte development. He/she will learn to apply advanced tissue engineering approaches from pluripotent stem cells and study the phenotypes using single-cell and epigenomic analysis methods.