On the origins and conceptual frameworks of natural plasticity-Lessons from single-cell models in C. elegans.

How flexible are cell identities? This problem has fascinated developmental biologists for several centuries and can be traced back to Abraham Trembley's pioneering manipulations of Hydra to test its regeneration abilities in the 1700s. Since the cell theory in the mid-19th century, developmental biology has been dominated by a single framework in which embryonic cells are committed to specific cell fates, progressively and irreversibly acquiring their differentiated identities. This hierarchical, unidirectional and irreversible view of cell identity has been challenged in the past decades through accumulative evidence that many cell types are more plastic than previously thought, even in intact organisms. The paradigm shift introduced by such plasticity calls into question several other key traditional concepts, such as how to define a differentiated cell or more generally cellular identity, and has brought new concepts, such as distinct cellular states. In this review, we want to contribute to this representation by attempting to clarify the conceptual and theoretical frameworks of cell plasticity and identity. In the context of these new frameworks we describe here an atlas of natural plasticity of cell identity in C. elegans, including our current understanding of the cellular and molecular mechanisms at play. The worm further provides interesting cases at the borderlines of cellular plasticity that highlight the conceptual challenges still ahead. We then discuss a set of future questions and perspectives arising from the studies of natural plasticity in the worm that are shared with other reprogramming and plasticity events across phyla.