Abstract
Stable cell fate is an essential feature for multicellular organisms in which individual cells achieve specialized functions. Caenorhabditis elegans is a great model to analyze the determinants of cell fate stability because of its invariant lineage. We present a tractable cell fate challenge system that uses the induction of fate-specifying transcription factors. We show that wild-type differentiated animals are highly resistant to fate challenge. Removal of heterochromatin marks showed marked differences: the absence of histone 3 lysine 9 methylation (H3K9) has no effect on fate stability, whereas Polycomb homolog mes-2 mutants lacking H3K27 methylation terminally arrest larval development upon fate challenge. Unexpectedly, the arrest correlated with widespread cell proliferation rather than transdifferentiation. Using a candidate RNAi larval arrest-rescue screen, we show that the LIN-12Notch pathway is essential for hyperplasia induction. Moreover, Notch signaling appears downstream of food-sensing pathways, as dauers and first larval stage diapause animals are resistant to fate challenge. Our results demonstrate an equilibrium between proliferation and differentiation regulated by Polycomb and Notch signaling in the soma during the nematode life cycle.
Highlights
During development, the differentiation potential of cells is progressively restricted, and differentiated cells have mostly lost their plasticity
As Notch signaling was previously shown to regulate entry and exit into the resistance stages of the nematode life cycle, we explored whether dauer and first larval stage animals in diapause are sensitive to cell fate challenge
Using a novel, tractable single-copy system for cell fate challenge insensitive to multicopy array heterochromatinization, we demonstrate with single-cell resolution that fully differentiated animals are highly resistant to transdifferentiation: only a single cell transiently expresses markers for the induced cell fate
Summary
The differentiation potential of cells is progressively restricted, and differentiated cells have mostly lost their plasticity. We show that cell fate is remarkably stable in fully differentiated animals of the first larval stage as only one cell is able to transiently express muscle markers. As Notch signaling was previously shown to regulate entry and exit into the resistance stages of the nematode life cycle, we explored whether dauer and first larval stage animals in diapause are sensitive to cell fate challenge. We find that these animals are completely resistant to transcription-factor–induced transdifferentiation; cell plasticity is highly reduced during these stages. Our experiments demonstrate that cell fate in differentiated animals is resistant to induction of muscle transdifferentiation
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