Fig. 5: A lack of FetuA increased vulnerability to leukaemogenesis.
From: Fetal hepatocytes protect the HSPC genome via fetuin-A
a, Experimental design for genome-wide R-loop sequencing (R-loop Cut&Tag), whole-genome sequencing (WGS) and leukaemia induction. b, Gene metaplots analysis of R-loop Cut&Tag. The mean coverages of R-loop signals over gene bodies (±1 kb) in E16.5 fetal liver HSPCs from WT and FKO mice are shown (n = 3). TSS, transcription start site; TES, transcription end site. c, Boxplots showing the R-loop signal over gene bodies (±1 kb) in E16.5 fetal liver HSPCs from WT and FKO mice (n = 3). The boxes delimit the lower (25th) and upper (75th) interquartile, and the horizontal line represents the median. d, The number of chromosomal insertions (left), deletions (middle) and structural variations (right) per genome in bone marrow HSPCs from 3-week-old Eto-treated WT and FKO mice at E16.5 (n = 4). The boxes delimit the minima and maxima, and the horizontal line represents the mean. e, Circos plots showing the genome-wide distribution of the identified R-loop events (outer circles; n = 3 per group) and mutations (inner circles; n = 4 per group) in HSPCs from WT and FKO mice. f, Dot plots revealing the correlation between R-loop signals and mutations in WT (left) and FKO (right) mice (n = 3 for R-loop and n = 4 for WGS). g, Mean R-loop signal (n = 3) and mutation numbers (n = 4) of the genes frequently involved in leukaemia in HSPCs from WT and FKO mice. h, The onset of leukaemia induced in WT and FKO mice by Eto treatment at E16.5 and N-ethyl-N-nitrosourea (ENU) treatment at 3 weeks of age (see Extended Data Fig. 4a; n = 6 for WT and n = 11 for FKO). The n represents individual samples (b–g) and mice (h) from three independent experiments. Two-sided Wilcoxon test (c), unpaired two-sided Student’s t-test (d), two-sided Pearson test (f) and log-rank (Mantel–Cox) test (h) were used.
