Search

Summary Cell-cell interactions shape cellular function and ultimately organismal phenotype. However, the spatial code embedded in the molecular interactions driving and sustaining spatial organization remains to be elucidated. Here we present a computational framework to infer the spatial code underlying cell-cell interactions in a whole animal. Using the transcriptomes of the cell types composing Caenorhabditis elegans’ body, we compute the potential for intercellular interactions from the coexpression of ligand-receptor pairs. Leveraging a 3D atlas of C. elegans’ cells and a genetic algorithm we identify the ligand-receptor pairs most informative of the spatial organization of cells. The resulting intercellular distances are negatively correlated with the potential for cell-cell interaction, validating this strategy. Further, for selected ligand-receptor pairs, we experimentally confirm the algorithm-generated cell-cell interactions. Thus, our computational framework helps identify a code associated with spatial organization and cellular functions across a whole-animal body, showing that single-cell molecular measurements provide spatial information that may help elucidate organismal phenotypes and disease. Highlights -A cell-cell interaction network in the whole body of C. elegans is presented. -Intercellular distance and interactions are negatively correlated. -A combination of ligand-receptor pairs carries a spatial code of cell-cell interactions. -Spatial expression of specific ligand-receptor pairs is validated in vivo. Graphical abstract

Aging is accompanied by unisensory decline; but to compensate for this, two complementary strategies are potentially relied upon increasingly: first, older adults integrate more information from different sensory organs. Second, according to predictive coding (PC) we form ‘templates’ (internal models or ‘priors’) of the environment through our experiences. It is through increased life experience that older adults may rely more on these templates compared to younger adults. Multisensory integration and predictive coding would be effective strategies for the perception of near-threshold stimuli, but they come at the cost of integrating irrelevant information. Their role can be studied in multisensory illusions because these require the integration of different sensory information, as well as an internal model of the world that can take precedence over sensory input. Here, we elicited a classic multisensory illusion, the sound-induced flash illusion, in younger (mean: 27 yrs) and older (mean: 67 yrs) adult participants while recording the magnetoencephalogram. Older adults perceived more illusions than younger adults. Older adults had increased pre-stimulus beta(β)-band activity compared to younger adults as predicted by microcircuit theories of predictive coding, which suggest priors and predictions are linked to β-band activity. In line with our hypothesis, transfer entropy analysis and dynamic causal models of pre-stimulus MEG data revealed a stronger illusion-related modulation of cross-modal connectivity from auditory to visual cortices in older compared to younger adults. We interpret this as the neural correlate of increased reliance on a cross-modal predictive template in older adults that is leading to the illusory percept.