What a natural reprogramming event tells us on the mechanisms underlying cellular plasticity
Whereas postmitotic somatic cellular identity is generally a stable feature of multicellular organisms, natural interconversions between functionally distinct somatic cell types (aka transdifferentiation or Td) have been reported in species as diverse as jellyfish and mice Direct reprogramming can also be induced experimentally, however at a very low frequency, and remains rare in vivo. Why do some cells but not their neighbours, change their identity? In some cases, Td events occur with remarkable precision and efficiency. For example, our laboratory has shown that a rectal cell suddenly loses its differentiated identity and is reprogrammed into a motoneuron with invariant precision, in 100% of the wild type Caenorhabditis elegans animals. We have further shown that this fascinating Td event proceeds through discrete steps in absence of cell division: dedifferentiation and then re-differentiation into the new cell type, similarly to vertebrate examples of Td, such as newt lens regeneration. We have used the rectal Y cell into the PDA motor neuron conversion, a defined, single cell, natural transdifferentiation event to investigate the mechanisms that ensure invariance and how extrinsic cues and the intrinsic context impact on the ability of a cell to change its identity. Our results support a model where both the microenvironment and the intrinsic cellular context combine to empower a cell with the competence to transdifferentiate. In addition, our findings emphasise the importance of the temporality and dynamics of the underlying molecular events preceding the initiation of natural cell fate conversion, as the same signals necessary to set up a competence to Td can, when provided out-of-time, block Td.
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Dr Olivia Casanueva
The Brian Heap Seminar Room