C. elegansの細胞発生を勉強すること

タイトル: Assessing the Relative Contributions of Mosaic and Regulatory Developmental Modes from Single-Cell Trajectories

概要: Development is a highly complex process consisting of coordinated cell proliferation, cell differentiation and spatial organization. Classically, two ways to specify cell types during development are hypothesized : mosaic and regulative modes. In the mosaic mode, a particular cell isolated from the rest of the embryo will nevertheless give rise to cells with a fate identical to the ones expected in normal development, thus relying on lineage-inherited factors. In the regulative mode, the fate of a cell depends on its interactions with its environment, and thus relies on space-dependant factors. Both modes often coexist in the development of a given animal. We propose to quantify their respective contributions from single-cell trajectories. C. elegans development provides a unique opportunity to elaborate such an approach. Indeed, its invariant lineage enables the integration of spatial positions, lineage relationships and protein expression data. Using the single cell protein expression profile as a readout of the cell state, we relate the contributions of the mosaic and the regulative modes to the following measurable quantities. The contribution of the mosaic mode, or lineage-inherited contribution is quantified by the strength of the relationship between the cell-cell lineage distance and the cell-cell expression distance. Similarly, the contribution of the regulative mode, or context-dependent contribution is quantified by the strength of the relationship between the cell-cell context distance and the cell-cell expression distance. The cell-cell context distance measures the similarity between the spatial neighborhoods of two cells based on the gene expression profiles of their neighbours. We assess the significance of these contributions by comparing the empirical results obtained on C. elegans data to artificial models generated using simple rules. With these measures, we show the co-existence of mosaic and regulative modes in the development of C. elegans. The relative contribution of these two modes varies across the different tissues and in time. In particular, we see in the skin tissue that during early development, the mosaic mode dominates while at later stages, regulative mode dominates, suggesting a convergence of single cell trajectories. These measures are general and can be applied to other datasets that will be made available with the progress of spatial transcriptomics and lineage-tracing, paving the way for a quantitative, unbiased and perturbation-free study of fundamental concepts in developmental biology.