Reconstruction of rat retinal progenitor cell lineages in vitro reveals a surprising degree of stochasticity in cell fate decisions

• DOI: 10.1242/dev.059683
• Publication Date: 2010-12-10T01:50:16Z
• Authors: Francisco L. A. F...; Gen Zhang; Felix Carbonell; José A. Correa; William A. Harris; Benjamin D. Simons; Michel Cayouette
• Keywords: Cell fate determination; Cell type; Lineage (genetic); Muller glia

In vivo cell lineage-tracing studies in the vertebrate retina have revealed that sizes and cellular compositions of retinal clones are highly variable. It has been challenging to ascertain whether this variability reflects distinct but reproducible lineages among many different progenitor cells (RPCs) or is product stochastic fate decisions operating within a population more equivalent RPCs. To begin distinguish these possibilities, we developed method for long-term videomicroscopy follow rat perinatal RPCs cultured at clonal density. such cultures, cell-cell interactions between two eliminated extracellular environment kept constant, allowing us study cell-intrinsic potential given RPC. Quantitative analysis reconstructed showed mode division strikingly consistent with simple pattern behavior which decision multiply differentiate set by fixed probabilities. The seen composition order type genesis well described assuming each four types generated stage chosen stochastically differentiating neurons, relative probabilities their abundance mature retina. Although few possible combinations occur frequencies incompatible fully model, our results support notion stochasticity major role during development therefore possibly other parts central nervous system.