Fig. 4
Genomic alterations associated with cell cycle in pre-leukemic stem cells (pre-LSCs). a Box plot of the relative expression profiling of genes in GFPlo and GFPhi DN3 thymocytes from H2B-GFP;Lmo2Tg mice 2 weeks after doxycycline pulse, in accordance with their chromosomal location. Median ± whiskers with maximum 1.5 interquartile range (IQR) and outliers are indicated for each chromosome. Log fold change (LogFC) as compared to median expression among all the samples analyzed. b Targeted probe analysis for chromosomes 15 and 2 in GFPlo DN3 thymocytes from H2B-GFP;Lmo2Tg mice 2 weeks after doxycycline pulse. Frequency of diploid (top panel) and aneuploid (bottom panel) cells is indicated. c Mouse chromosomal ideogram showing the chromosomal gain and losses identified in GFPlo subpopulations of DN3 thymocytes by whole-exome sequencing (WES) on 5 individual doxycycline-pulsed 2-month-old H2B-GFP;Lmo2Tg mice. Top red bars represent chromosomal gains and losses are identified by bottom blue bars. d Diagram showing the position of mutations found in the Notch1 gene sequence in purified GFPhi DN3 thymocytes from 2-month old H2B-GFP;Lmo2Tg mice (n = 5). The amino-acid numbers are shown, with their position in the corresponding exons from the Notch1 locus. GFP green fluorescent protein, L Lin/NOTCH repeats, T transmembrane domain, RAM RAM domain, ANK ankyrin repeat domain, TAD transactivation domain, PEST PEST domain; and the arrow indicated the site of cleavage releasing the Notch1 intracellular domain following activation
