Our research focuses on understanding the development of mammalian primordial germ cells (PGCs), the precursors of sperm or egg. PGCs represent the only cell type that transmits genetic and epigenetic information to the next generation. In mammals, the developing embryo forms the postimplantation epiblast, the founder cell population of all embryonic cell types. While most of these cells give rise to organs and tissues, a few are specified to become PGCs. Shortly after, PGCs undergo reprogramming including extensive transcriptional changes accompanied by epigenetic alterations. Our work addresses the questions: Which genes and proteins are required for PGC development? How is the transcriptional programme controlled during differentiation of PGCs? To address these questions, we make use of in vivo and in vitro model systems of PGC differentiation, genome-wide techniques and the CRISPR/Cas9 genome editing tool.
Research on PGCs has gained a lot of attention in recent years, since it is now possible to generate PGC-like cells (PGCLCs) from embryonic stem cells (ESCs) or from induced pluripotent stem cells (iPSCs) in vitro. For example, mouse ESCs are differentiated into epiblast-like cells (EpiLCs), which are very similar to the epiblast of the early postimplantation embryo. Accordingly, these cells can be efficiently induced into functional PGCLCs, which can be further differentiated towards eggs or sperm. However, it is important to note that there are key differences between mouse and human PGC development. Therefore, we make use of in vitro systems for mouse, primate and human PGCLCs, to study the specification and differentiation of PGCs in mammals.
When PGCs arise in the postimplantation embryo, initially a few key transcription factors are upregulated. These factors control the activity of specific sets of genes establishing the transcriptional network of PGCs. To understand the mechanisms driving these changes, we are particularly interested in enhancer elements, which are non-coding DNA elements. Enhancers serve as platforms for transcription factor recruitment, thereby activating or enhancing transcription from gene promoters. These cis-regulatory elements enable spatial and temporal regulation of gene expression, thus acting as “drivers” of developmental processes. We make use of genome-wide techniques to identify enhancers and the genome editing tool CRISPR/Cas9 to characterise their cell-type specific roles during PGC differentiation.
|Stefan Schoenfelder||Babraham Institute, Cambridge||Transcriptional regulation in PGCs|
|Rüdiger Behr||German Primate Center, Göttingen||PGC differentiation in non-human primates|