Supplementary Figure 7: Cell dynamics in Ras- driven SCCs.
From: A single dividing cell population with imbalanced fate drives oesophageal tumour growth
(a,b) Representativeness of clones in SCC in AhcreERTRosa26flYFP/wtKrasflG12D/wt animals, induced after DEN exposure and before Sorafenib treatment as shown in Fig. 8a. (a) Mean percentage EdU + cells, 1 h after labelling, in whole tumours and YFP + clones within them, n.s. P = 0.69 by Kolmogorov-Smirnov test, n = 23 clones from 3 tumours. (b) Mean percentage Ki67 + cells in whole tumours and clones within them, n.s. P = 0.34 by two tailed t-test, n = 12 clones from 4 tumours. (c,d) Clone size distributions 56 days after induction. Points are experimental data, lines model predictions and blue area shows standard deviation of the prediction. Data is binned in intervals of 10 cells per clone (c) and 100 cells per clone (d), respectively. (c) Clones <200 cells (n = 25 clones), 56 days after induction, shown with model prediction derived from HGD lesions (see Fig. 7d). (d) Rescaled clone size distribution for clones > 200 cells (n = 16 clones), at 56 days after induction, together with theoretical prediction (exponential function), see Supplementary Note 2.4 for discussion. (e) Cryosection of SCC stained for proliferation marker Ki67 (green) and basal cell marker ITGA6 (white). Scale bar, 100 μm and 50 μm, respectively. Image is representative of 4 tumours. (f) Summary: proliferating cell fate in oesophageal carcinogenesis. In histologically normal epithelium, even after exposure to nitrosamine and Sorafenib, cell production (green arrow) equals cell loss (red arrow). Proliferating cell fate is balanced, generating equal proportions of dividing and non-dividing cells on average. In tumours, an excess of dividing cells is generated locally. This is achieved through a small bias in cell fate towards producing proliferating progeny, Δ, and a reduction in the rate of cell loss relative to cell production.
