Evidence for close molecular proximity between reverting and undifferentiated cells.

BACKGROUND: According to Waddington's epigenetic landscape concept, the differentiation process can be illustrated by a cell akin to a ball rolling down from the top of a hill (proliferation state) and crossing furrows before stopping in basins or "attractor states" to reach its stable differentiated state. However, it is now clear that some committed cells can retain a certain degree of plasticity and reacquire phenotypical characteristics of a more pluripotent cell state. In line with this dynamic model, we have previously shown that differentiating cells (chicken erythrocytic progenitors (T2EC)) retain for 24 h the ability to self-renew when transferred back in self-renewal conditions. Despite those intriguing and promising results, the underlying molecular state of those "reverting" cells remains unexplored. The aim of the present study was therefore to molecularly characterize the T2EC reversion process by combining advanced statistical tools to make the most of single-cell transcriptomic data. For this purpose, T2EC, initially maintained in a self-renewal medium (0H), were induced to differentiate for 24H (24H differentiating cells); then, a part of these cells was transferred back to the self-renewal medium (48H reverting cells) and the other part was maintained in the differentiation medium for another 24H (48H differentiating cells). For each time point, cell transcriptomes were generated using scRT-qPCR and scRNAseq. RESULTS: Our results showed a strong overlap between 0H and 48H reverting cells when applying dimensional reduction. Moreover, the statistical comparison of cell distributions and differential expression analysis indicated no significant differences between these two cell groups. Interestingly, gene pattern distributions highlighted that, while 48H reverting cells have gene expression pattern more similar to 0H cells, they are not completely identical, which suggest that for some genes a longer delay may be required for the cells to fully recover. Finally, sparse PLS (sparse partial least square) analysis showed that only the expression of 3 genes discriminates 48H reverting and 0H cells. CONCLUSIONS: Altogether, we show that reverting cells return to an earlier molecular state almost identical to undifferentiated cells and demonstrate a previously undocumented physiological and molecular plasticity during the differentiation process, which most likely results from the dynamic behavior of the underlying molecular network.

Selective neural coding of object, feature, and geometry spatial cues in humans.

Orienting in space requires the processing of visual spatial cues. The dominant hypothesis about the brain structures mediating the coding of spatial cues stipulates the existence of a hippocampal-dependent system for the representation of geometry and a striatal-dependent system for the representation of landmarks. However, this dual-system hypothesis is based on paradigms that presented spatial cues conveying either conflicting or ambiguous spatial information and that used the term landmark to refer to both discrete three-dimensional objects and wall features. Here, we test the hypothesis of complex activation patterns in the hippocampus and the striatum during visual coding. We also postulate that object-based and feature-based navigation are not equivalent instances of landmark-based navigation. We examined how the neural networks associated with geometry-, object-, and feature-based spatial navigation compared with a control condition in a two-choice behavioral paradigm using fMRI. We showed that the hippocampus was involved in all three types of cue-based navigation, whereas the striatum was more strongly recruited in the presence of geometric cues than object or feature cues. We also found that unique, specific neural signatures were associated with each spatial cue. Object-based navigation elicited a widespread pattern of activity in temporal and occipital regions relative to feature-based navigation. These findings extend the current view of a dual, juxtaposed hippocampal-striatal system for visual spatial coding in humans. They also provide novel insights into the neural networks mediating object versus feature spatial coding, suggesting a need to distinguish these two types of landmarks in the context of human navigation.

Landmark-based spatial navigation across the human lifespan.

Human spatial cognition has been mainly characterized in terms of egocentric (body-centered) and allocentric (world-centered) wayfinding bhavior. It was hypothesized that allocentric spatial coding, as a special high-level cognitive ability, develops later and deteriorates earlier than the egocentric one throughout lifetime. We challenged this hypothesis by testing the use of landmarks versus geometric cues in a cohort of 96 deeply phenotyped participants, who physically navigated an equiangular Y maze, surrounded by landmarks or an anisotropic one. The results show that an apparent allocentric deficit in children and aged navigators is caused specifically by difficulties in using landmarks for navigation while introducing a geometric polarization of space made these participants as efficient allocentric navigators as young adults. This finding suggests that allocentric behavior relies on two dissociable sensory processing systems that are differentially affected by human aging. Whereas landmark processing follows an inverted-U dependence on age, spatial geometry processing is conserved, highlighting its potential in improving navigation performance across the lifespan.