Abstract
Dedifferentiation is a critical response to tissue damage, yet is not well understood, even at a basic phenomenological level. Developing Dictyostelium cells undergo highly efficient dedifferentiation, completed by most cells within 24 hr. We use this rapid response to investigate the control features of dedifferentiation, combining single cell imaging with high temporal resolution transcriptomics. Gene expression during dedifferentiation was predominantly a simple reversal of developmental changes, with expression changes not following this pattern primarily associated with ribosome biogenesis. Mutation of genes induced early in dedifferentiation did not strongly perturb the reversal of development. This apparent robustness may arise from adaptability of cells: the relative temporal ordering of cell and molecular events was not absolute, suggesting cell programmes reach the same end using different mechanisms. In addition, although cells start from different fates, they rapidly converged on a single expression trajectory. These regulatory features may contribute to dedifferentiation responses during regeneration.
Highlights
Dedifferentiation is the transition of a cell to a state characteristic of an earlier stage of development
Structures were gently disaggregated to single cells, which were inoculated into different types of growth media, or into phosphate buffer lacking nutrients
When compared to mammalian dedifferentiation contexts, the dedifferentiation response of Dictyostelium cells is remarkable in its speed and reliability, with most cells reversing their development in around 24 hr, whilst retaining their ability to generate a full complement of cell fates upon re-induction of development
Summary
Dedifferentiation is the transition of a cell to a state characteristic of an earlier stage of development. Triggered dedifferentiation is central to approaches to generate induced pluripotent stem cells (IPSCs) for tissue repair strategies (Takahashi and Yamanaka, 2016). Despite these important biological and clinical contexts, dedifferentiation is not well understood in any system – it would be fair to say that we do not even have an approximate conceptual framework for the main features of the process. The possibility of a stereotypical programme has been the subject of some debate, with some evidence for multiple gene expression trajectories, at least during IPSC derivation (Stuart et al, 2019) It is not clear whether dedifferentiation should be considered as regulated in the sense of having checkpoints, monitoring the gradual activation of the necessary changes that make a stem cell
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