# Antagonistic roles of Polycomb repression and Notch signaling in the maintenance of somatic cell fate in C. elegans.

## TL;DR

This paper explores how Polycomb repression and Notch signaling interact to maintain or change cell fate in C. elegans larvae.

## Contribution

The study reveals an antagonistic relationship between Polycomb repression and Notch signaling in regulating cell plasticity.

## Key findings

- Polycomb-associated H3K27 methylation stabilizes cell fate in differentiated larvae.
- Notch signaling rescues developmental arrest caused by loss of Polycomb repression.
- Increased Notch signaling makes cells more sensitive to transdifferentiation.

## Abstract

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.