From single cells to tissue self-organization.

Self-organization is a process by which interacting cells organize and arrange themselves in higher order structures and patterns. To achieve this, cells must have molecular mechanisms to sense their complex local environment and interpret it to respond accordingly. A combination of cell-intrinsic and cell-extrinsic cues are decoded by the single cells dictating their behaviour, their differentiation and symmetry-breaking potential driving development, tissue remodeling and regenerative processes. A unifying property of these self-organized pattern-forming systems is the importance of fluctuations, cell-to-cell variability, or noise. Cell-to-cell variability is an inherent and emergent property of populations of cells that maximize the population performance instead of the individual cell, providing tissues the flexibility to develop and maintain homeostasis in diverse environments. In this review, we will explore the role of self-organization and cell-to-cell variability as fundamental properties of multicellularity-and the requisite of single-cell resolution for its understanding. Moreover, we will analyze how single cells generate emergent multicellular dynamics observed at the tissue level 'travelling' across different scales: spatial, temporal and functional.