Wt1 heterozygous loss has an age-dependent impact on genetic/epigenetic landscape. Normalized enrichment scores of gene signatures defined by RNA-seq performed in MPs from young chronic and young acute heterozygous mice compared with age-matched controls (A) or young controls (B) and between heterozygous mice from each subgroup (young vs old) (upper panel). (A-B) Normalized counts of a subset of genes differentially expressed in Wt1-heterozygote sorted MPs compared with controls (lower panel). (C) Serial replating assay of control (EV) or ectopic Gata1-, Npm1-, or shCebpa-expressing Wt1^fl/+ BM cells from the young chronic cohort. Representative results of 3 independent experiments, each performed in triplicate. Data are mean ± standard error of the mean. (D) CHIP-seq signals for Wt1 at Gata1, Npm1, and Cebpa loci. *P < .05, **P < .01, ***P < .001, ****P < .0001, 2-way analysis of variance.