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Tumorigenic cells
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CSCs
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Any cell
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Tumor cell organization
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Hierarchical
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Stochastic
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Capacity of self-renewal with asymmetric divisions
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CSCs can self-renew indefinitely whereas terminally differentiated cells have limited proliferative potential
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Not applicable
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Progression
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Driven by CSCs, which account for a small subpopulation of the tumor bulk
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Driven by the fittest clone under a constellation of selective pressures
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Source of heterogeneity
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Aberrant differentiation program and mutations
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Epigenetic and genetic aberrations followed by selection
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Type of heterogeneity
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Initially perceived as largely phenotypic; however, more recent studies suggested that CSCs may be genetically heterogeneous within a tumor
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Genetic and phenotypic heterogeneity
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Source of resistance to therapy
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CSCs
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Selection of resistant subclones harboring specific genetic or epigenetic aberrations
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