Abstract
During tissue and organ development and maintenance, the dynamic regulation of cellular proliferation and differentiation allows cells to build highly elaborate structures. The development of the vertebrate retina or the maintenance of adult intestinal crypts, for instance, involves the arrangement of newly created cells with different phenotypes, the proportions of which need to be tightly controlled. While some of the basic principles underlying these processes developing and maintaining these organs are known, much remains to be learnt from how cells encode the necessary information and use it to attain those complex but reproducible arrangements. Here, we review the current knowledge on the principles underlying cell population dynamics during tissue development and homeostasis. In particular, we discuss how stochastic fate assignment, cell division, feedback control and cellular transition states interact during organ and tissue development and maintenance in multicellular organisms. We propose a framework, involving the existence of a transition state in which cells are more susceptible to signals that can affect their gene expression state and influence their cell fate decisions. This framework, which also applies to systems much more amenable to quantitative analysis like differentiating embryonic stem cells, links gene expression programmes with cell population dynamics.
Highlights
The total number of cells of an organism is a tightly regulated variable
We review the current knowledge on the dynamics of cell populations during homeostasis, highlight recent findings on universal patterns associated with this process and explore whether and how can these be extrapolated to developing tissues
The first one is exemplified by eutelic organisms like C. elegans, in which every division is associated with the generation of two different cells and this process is iterated over time (Sulston, 1976; Sulston & Horvitz, 1977)
Summary
The total number of cells of an organism is a tightly regulated variable. For instance, a human being contains more than 1013 cells (Bianconi et al, 2013), while a male Caenorhabditis elegans nematode worm is composed of exactly 1,031 cells (Sulston, 1976; Sulston & Horvitz, 1977). The number of divisions is exquisitely regulated, such that each tissue is the result of a defined lineage built from a sequence of asymmetric cell divisions, that is, each gives rise to two different cells, and underpinned by a hardwired genetic programme (Gonczy, 2008; Knoblich, 2008). This strategy can be found in other systems like the embryonic central neural system (CNS) of insects (Kohwi & Doe, 2013) where each neuroblast.
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