PT  - JOURNAL ARTICLE
AU  - Ringo Pueschel
AU  - Francesca Coraggio
AU  - Alisha Marti
AU  - Peter Meister
TI  - Antagonistic roles of Polycomb repression and Notch signaling in the maintenance of somatic cell fate in <em>C. elegans.</em>
AID  - 10.1101/055137
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 055137
4099  - http://biorxiv.org/content/early/2016/06/02/055137.short
4100  - http://biorxiv.org/content/early/2016/06/02/055137.full
AB  - Reprogramming of somatic cells in intact nematodes allows characterization of cell plasticity determinants, which knowledge is crucial for regenerative cell therapies. By inducing muscle or endoderm transdifferentiation by the ectopic expression of selector transcription factors, we show that cell fate is remarkably robust in fully differentiated larvae. This stability depends on the presence of the Polycomb-associated histone H3K27 methylation, but not H3K9 methylation: in the absence of this epigenetic mark, many cells can be transdifferentiated which correlates with definitive developmental arrest. A candidate RNAi screen unexpectedly uncovered that knock-down of somatic NotchLIN-12 signaling rescues this larval arrest. Similarly in a wild-type context, genetically increasing NotchLIN-12 signaling renders a fraction of the animals sensitive to induced transdifferentiation. This reveals an antagonistic role of the Polycomb repressive complex 2 stabilizing cell fate and Notch signaling enhancing cell plasticity.