Journal: PLoS ONE
Article Title: Intrinsic growth heterogeneity of mouse leukemia cells underlies differential susceptibility to a growth-inhibiting anticancer drug
doi: 10.1371/journal.pone.0236534
Figure Lengend Snippet: (A and B) Schematic representation of the device. (A) The top view of the device. The culture medium flows through the trench (white arrows). Cells trapped in the growth channels are observed simultaneously by time-lapse imaging. (B) A cross-section of the device at the plane corresponding to the broken line indicated by the black arrows in (A). The height and the width of a growth channel are both 20 μm, which corresponds to the size of L1210 cells. (C) A micrograph of L1210 cells in the device. (D) Tracing individual L1210 cell lineages. Twenty representative single-cell lineages of L1210 cells cultured in a constant environment are shown. Each horizontal line represents a single-cell lineage, and the points represent the time points at which cell division occurred. The blue cell lineages are fast-cycling cell lineages, which divided 12 times or more during the seven-day culture; the red cell lineages are slow-cycling cell lineages, which divided 11 times or less during the same period. Co-existence of the heterogeneous growth phenotype is further discussed in the main text. (E) Constant division rate. At each time point t , we estimated an instantaneous cell division probability as D ( t ) N ( t ) , where N ( t ) is the number of surviving cells, and D ( t ) is the number of cells that underwent cell division within the time-lapse interval ( t , t + Δ t ]. Δ t is 10 min throughout this study. The vertical axis is the cumulative sum of instantaneous division probability, i.e., ∑ t ′ = 0 t D ( t ′ ) N ( t ′ ) . Blue points represent the experimental data. The black broken-line is the line of linear fit; the slope is (9.033±0.003) × 10 −2 h −1 . The cumulative sum of division probability increases linearly with t , which indicates that the division rate was constant throughout the observation period. (F) Constant death rate. The fraction of surviving cell lineages was plotted over time with the vertical axis on the log scale. Blue points are the experimental data. Black broken-line is the line of linear fit; the slope is −(2.239±0.009) × 10 −3 h −1 . The surviving fraction decreased in an exponential manner, which indicated a constant death rate throughout the observation period.
Article Snippet: L1210 mouse lymphocytic leukemia cells were purchased from ATCC (ATCC CCL-219).
Techniques: Imaging, Cell Culture