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

被引:121
作者
Gomes, Francisco L. A. F. [1 ]
Zhang, Gen [2 ]
Carbonell, Felix [3 ]
Correa, Jose A. [4 ]
Harris, William A. [5 ]
Simons, Benjamin D. [2 ,6 ]
Cayouette, Michel [1 ,7 ,8 ,9 ]
机构
[1] Inst Rech Clin Montreal, Cellular Neurobiol Res Unit, Montreal, PQ H2W 1R7, Canada
[2] Univ Cambridge, Cavendish Lab, Dept Phys, Cambridge CB3 0HE, England
[3] McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ H3A 2B4, Canada
[4] McGill Univ, Dept Math & Stat, Montreal, PQ H3A 2K6, Canada
[5] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3DY, England
[6] Univ Cambridge, Wellcome Trust Canc Res UK Gurdon Inst, Cambridge CB2 1QN, England
[7] Univ Montreal, Dept Med, Montreal, PQ H3T 3J7, Canada
[8] McGill Univ, Dept Biol, Dept Anat & Cell Biol, Montreal, PQ H3A 1B1, Canada
[9] McGill Univ, Div Expt Med, Montreal, PQ H3A 1B1, Canada
来源
DEVELOPMENT | 2011年 / 138卷 / 02期
基金
英国工程与自然科学研究理事会; 加拿大健康研究院; 英国惠康基金;
关键词
Cell fate choice; Lineage; Live imaging; Retina; Rat; NEURAL REGENERATION; MICE LACKING; MULLER GLIA; COMPETENCE; HYPERPLASIA; DIVISIONS; MIGRATION; NEMATODE;
D O I
10.1242/dev.059683
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
In vivo cell lineage-tracing studies in the vertebrate retina have revealed that the 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 retinal progenitor cells (RPCs) or is the product of stochastic fate decisions operating within a population of more equivalent RPCs. To begin to distinguish these possibilities, we developed a method for long-term videomicroscopy to follow the lineages of rat perinatal RPCs cultured at clonal density. In such cultures, cell-cell interactions between two different clones are eliminated and the extracellular environment is kept constant, allowing us to study the cell-intrinsic potential of a given RPC. Quantitative analysis of the reconstructed lineages showed that the mode of division of RPCs is strikingly consistent with a simple stochastic pattern of behavior in which the decision to multiply or differentiate is set by fixed probabilities. The variability seen in the composition and order of cell type genesis within clones is well described by assuming that each of the four different retinal cell types generated at this stage is chosen stochastically by differentiating neurons, with relative probabilities of each type set by their abundance in the mature retina. Although a few of the many possible combinations of cell types within clones occur at frequencies that are incompatible with a fully stochastic model, our results support the notion that stochasticity has a major role during retinal development and therefore possibly in other parts of the central nervous system.
引用
收藏
页码:227 / 235
页数:9
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