Figure 6

Hierarchy of cell heterogeneity.

(A) Images of PAC01 and PAC09 cells after four-day growth from a sparse initial seeding density and show cells forms several spatially and morphologically distinct progenies. Detailed view of cell images in highlighted areas are shown in the bottom. (B) Paired correlation analysis of nucleus size and cell size for PAC01 and PAC09 cells. Elevated correlation for cells in proximity was found in both all population and cells in G₀/G₁ phase. After randomly permutation label cells, this correlation disappears. (C) Bar graphs show the average variances of nucleus size and cell size among different pancreatic cancer cells, including PAC01, PAC02, PAC03, PAC04, PAC06, PAC07, PAC08 and PAC09. Variance of cells depends on the underlying cellular conditions including singlet, crowding, in the G₀/G₁ phase, in the G₂/M phase. Averaged nucleus size and cell size variation within a clone (<σ_p²>) for all cells and for cells in the G₀/G₁ phase is also shown. The variances are scaled by the variance among all populations. Great decrease in variations in both nucleus size and cell size were found for clonal cells in the G₀/G₁ phase. The P value is calculated using one-way ANOVA. (D) A plot illustrates that observed cell heterogeneity are combination of different effects including cell cycle, cell-cell contact, cell stochasticity and heritable cell variation. A proposed mathematical model to describe cellular heterogeneity is shown in the bottom. (E) CV of averaged nucleus size and averaged cell size among different progenies is used to measure heritable variation for both LM (PAC01~PAC04) and PT (PAC06 ~ PAC09). LM display in average lower heritable variation in both nucleus size (P < 0.05) and cell size (P > 0.05). The P value is calculated based on two-sample t-test.