From single cells to tissue self‐organization

Abstract

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.

Bioinspired Precision Engineering of Three‐Dimensional Epithelial Stem Cell Microniches

“…Maintenance of tissue homeostasis requires spatiotemporal cell organization to ensure tissue function. [ 35 ] While replicating the geometry and dimensions of the stem cell niche has a major influence over cell phenotype, as we report herein, cellular organization and phenotype within the niche is also influenced by other factors. Another potential parameter is the topography at the base.…”

Systematic genetics and single‐cell imaging reveal widespread morphological pleiotropy and cell‐to‐cell variability

“…In fact, for the majority of mutants, variability in morphological phenotypes between individual cells in an isogenic cell population is likely not driven solely by a genotype‐to‐phenotype relationship, but rather by a combination of smaller contributions from various effects that impact single cells differently depending on their physiological state. A deeper understanding of this variability may also have broad medical implications and should provide insight into the variable penetrance of genes affecting developmental programs and disease genes (Cooper et al , ; Kammenga, ; Li et al , ; Xavier da Silveira Dos Santos & Liberali, ).…”

Exploring single cells in space and time during tissue development, homeostasis and regeneration

“…During development, populations of cells interact and coordinate their behaviors in space and time to generate, bottom up, tissues and organs without a pre-defined blueprint (Bryant and Mostov, 2008;Gilmour et al, 2017;O'Brien et al, 2002). In particular, cells integrate complex intracellular and extracellular cues, both chemical and mechanical, and make individual decisions with respect to cell proliferation, differentiation or migration that, at the population level, lead to emergent processes such as tissue morphogenesis, homeostasis and regeneration (Bryant and Mostov, 2008;Chau et al, 2012;Sasai, 2013; Xavier da Silveira Dos Santos and Liberali, 2018). To achieve this, single cells have evolved different molecular and cellular mechanisms to sense neighboring cells and their local environment, and to regulate numerous biological features such as the cell cycle, cell shape, gene expression and polarization (Bryant and Mostov, 2008;Kim et al, 2018;Snijder and Pelkmans, 2011).…”