Epigenetic mechanisms that define the exit from pluripotency

• Antragsteller: Professor Dr. Heiko Lickert; Professor Dr. Gunnar Schotta
• Fachliche Zuordnung: Zellbiologie
• Förderung: Förderung von 2011 bis 2015
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 195123006

Mouse embryonic stem (ES) cells are pluripotent and have the potential to generate all cell lineages of an embryo. Loss of pluripotency during gastrulation coincides with the differentiation of the three germ-layers: endoderm, ectoderm and mesoderm. When cells have made a lineage commitment, transcription programs stably change by epigenetic mechanisms. This means that in homeostasis and under normal physiological conditions most differentiated cell types are unable to dedifferentiate and to change fate to other cell lineages. Formally, reprogramming is possible by nuclear cloning or by forced expression of pluripotency-associated transcription factors, however, these techniques are low-efficient, supporting the hypothesis that epigenetic mechanisms have the potential to stabilize transcription programs. It is currently unclear at what stage of lineage commitment, undifferentiated cells lose their pluripotency. Also the epigenetic mechanisms that mediate this transition are largely unknown. In this proposal we will address the epigenetic mechanisms that define the exit from pluripotency using a well-defined mesendoderm differentiation system, which precisely reflects the situation in the gastrulating mouse embryo. We will combine in vivo tests for pluripotency with analyses of epigenetic and transcriptional changes at defined stages after triggering pluripotency exit. These analyses will reveal novel insights into how pluripotency is controlled on the transcriptional and epigenetic level and how distinct signaling pathways utilize epigenetic mechanisms to trigger exit of pluripotency and stabilize a commitment program.

• DFG-Verfahren: Schwerpunktprogramme
• Teilprojekt zu: SPP 1356: Pluripotency and Cellular Reprogramming