In vivo cellular plasticity and direct reprogramming

There is more to cells than meets the eye !!! While most differentiated cells maintain their specialized identity their whole life, some change their identity and become something else: this is fascinating !!! We focus on direct reprogramming, the process where a differentiated cell swaps its identity to become another kind of differentiated cell (aka Transdifferentiation; check out our Lambert at al, 2021 article for a more philosophical discussion of cellular identity).

How can this happen, and especially how can this happen naturally in a range of species ? Numerous examples of cellular plasticity in physiological, experimental and pathological settings exist, but precisely how a differentiated cell can change its identity remains unclear. Work in the lab aims at exploring the many questions triggered by such phenomenon : What enables a cell to change it its identity and what steps and cellular trajectory are at play ? How similar are different reprogramming processes ? Does this happen only in specific cells ? Are there mechanisms to suppress reprogramming in other cells ? How is this influenced by the environment ?

To tackle these important questions we established a powerful and innovative model, looking at natural direct reprogramming events in vivo, at the single cell level, in the nematode C. elegans. For example, we have dissected how a rectal cell changes its identity into a moto-neuron. Because of the C. elegans invariant cellular lineage, our system gives us access to all the steps of the process, including the early ones, a unique asset. We have begun the systematic identification of the molecular networks and the dissection of the cellular requirements underlying several direct cell type conversion in vivo, and use a combination of genetics (mutants and RNAi), imaging, genome recombineering (CRISPR-Cas9), biochemical and transcriptomics (single cell RNA Seq) approaches.

Our integrated approaches will contribute to unravel not only key mechanisms that allow a differentiated cell to become plastic and change its identity, but also fundamental principles governing cellular identity maintenance & reprogramming. Such knowledge has significant therapeutic implications, as it will deepen our understanding of the initiation of certain cancers, and will improve our ability to reprogram cells for regenerative medicine purposes.

You would like to solve the next questions in cellular plasticity ? We welcome spontaneous applications all year round (sophie@igbmc.fr)