Cell and molecular transitions during efficient dedifferentiation

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.

Decanoic acid inhibits mTORC1 activity independent of glucose and insulin signaling

“…In order to monitor the effects of decanoic acid and octanoic acid on mTORC1 signaling in Dictyostelium , we quantified levels of phosphorylated 4E-BP1 (p-4E-BP1), a translation repressor directly phosphorylated by mTORC1 ( Fig. 1 A ) ( 38 , 39 ). Concentrations of decanoic acid and octanoic acid corresponding to an ∼95% reduction in growth rate (60 and 120 µM, respectively) ( Fig.…”

“…S2 G ). We also evaluated the effect of decanoic acid on AMPK signaling by assessing phospho-AMPKα (p-AMPK) levels ( 39 , 48 ) ( SI Appendix , Fig. S2 H – K ), where no significant difference was observed ( Fig.…”

Social Conflicts in <em>Dictyostelium discoideum</em> : A Matter of Scales

“…Observations of vegetative cells, on the other hand, show that motility can change relatively rapidly in time, and reflect the rate of encounters with other cells (d'Alessandro et al, 2018). Moreover, recent observations of cells from disaggregated slugs observed two sub-populations moving at different speed, but these did not correspond to prestalk and pre-spore sub-populations (Nichols et al, 2020).…”

“…For instance, if one part of a slug is experimentally removed, cell fate decision are reassessed (Raper, 1940). Similarly, once extracted from their social context by dissolving a slug into fresh medium, cells de-differentiate and resume unicellular growth (Soll & Waddell, 1975) in a way that is highly robust to mutations in developmental genes (Nichols et al, 2020).…”

“…Strain-level decisions would then be dictated by 'strategic' celllevel choices within one single generation rather than by long-term evolutionary processes (Madgwick et al, 2018). Just recently, molecular tools have been used to start examining how such decision-making is implemented during the process of aggregation and development (Gruenheit et al, 2018;Nichols et al, 2020).…”