Biology subjects

Ozier-Lafontaine, A.

Publications and source records attributed to Ozier-Lafontaine, A..

4 recordsLinked to original sources

bioRxiv2026

Kontext: Kernel-based method bridging spatial domain identification and cell-cell communication

The spatial organization of biological tissues is characterized by spatial domains: regions with coherent transcriptional and anatomical properties, heavily influenced by local cell-cell interactions. Although identifying spatial domains is a common task in spatial transcriptomics, most existing methods provide limited mechanistic insight into their organization. We present Kontext, a kernel-based framework that jointly represents cells and their local environments, enabling the identification of spatial domains grounded in their underlying ligand-receptor interactions. This representation further provides complementary outputs for characterizing cellular microenvironments, spatial niches, and sender-receiver communication patterns. Kontext outperforms state-of-the-art methods in recovering reference domain annotations across several spatial transcriptomics technologies and biological models, while offering improved computational efficiency and scalability. Applying Kontext on a Xenium temporal mouse heart cryoinjury dataset, we characterize the spatiotemporal evolution of the injury and identify an undescribed sustained activity of the complement system in the communication between fibroblasts and macrophages during scar maturation. In a million-cell three-dimensional Open-ST dataset of human metastatic lymph node tissue, we combine spatial domain identification and niche analysis to define the boundary region between the tumor and its microenvironment, revealing distinct communication patterns between this interface and the tumor core.

bioinformatics↗

bioRxiv2022

Evidence for close molecular proximity between reverting and undifferentiated cells

According to Waddingtons 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 hours 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. 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 retained traces of their engagement in the differentiation process. Finally, Sparse PLS analysis showed that only the expression of 3 genes discriminates 48H reverting and 0H cells. 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.

cell biology↗

bioRxiv2021

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

Orienting in space requires the processing and encoding 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 amalgamated the concept of landmark into both discrete 3D objects and wall features. These confounded designs introduce difficulties in interpreting the spatial learning process. Here, we test the hypothesis of a complex interaction between the hippocampus and the striatum during landmark and geometry visual coding in humans. We also postulate that object-based and feature-based navigation are not equivalent instances of landmark-based navigation as currently considered in human spatial cognition. We examined the neural networks associated with geometry-, object-, and feature-based spatial navigation in an unbiased, two-choice behavioral paradigm using fMRI. We showed evidence of a synergistic interaction between hippocampal and striatal coding underlying flexible navigation behavior. 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. Critically, object-based navigation elicited a widespread pattern of activity in temporal and occipital regions relative to feature-based navigation. These findings challenge and 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 vs. feature spatial coding, suggesting a need to distinguish these two types of landmarks in the context of human navigation. Highlights O_LIComplex hippocampal-striatal interaction during visual spatial coding for flexible human navigation behavior. C_LIO_LIDistinct neural signatures associated with object-, feature-, and geometry-based navigation. C_LIO_LIObject- and feature-based navigation are not equivalent instances of landmark-based navigation. C_LI

neuroscience↗

bioRxiv2020

Modulation of spatial cue processing across the lifespan: a geometric polarization of space restores allocentric navigation strategies in children and older adults

The impact of development and healthy aging on spatial cognition has been traditionally attributed to a difficulty in using allocentric strategies and a preference for egocentric ones. An alternative possibility, suggested by our previous works, is that this preference is actually conditioned by the spatial cues (e.g. geometric of landmark cues) present in the environment rather than a strategic choice per se. We tested this prediction by having 79 subjects (children, young and older adults) navigating a Y-maze composed either of landmarks or geometric cues, with an immersive head-mounted display that allows us to record both head and eye movements. Our results show that when the performance is based on landmarks solely, children and older adults exhibit a deficit in using allocentric strategies when compared to young adults. Hence, an inverted U-profile of allocentric strategies was observed across the lifespan. This was not due to a default of attention to the landmarks, as evidenced by analysis of gaze dynamics. When geometric were provided, however, older adults and children used allocentric strategies in the same proportion as young adults. They were, in addition, as efficient and quick to implement the strategy. We thus propose a reinterpretation of the previous data in the literature, whereby reference to geometric cues is the default mode for spatial representations, which is immune to age, whereas spatial representations fail to be anchored on landmarks early in development and later in aging. This new interpretation has the potential to reunify several data from the literature, ranging from spatial cues processing to strategy preference, and including other spatial skills like path integration and route learning.

neuroscience↗