LSC enhancers characterize cell identity and are functionally important for maintaining LSC oncogenic potential. (A) Ranked enhancer plots defined across composite H3K27ac landscapes of GMP, LSC, and mAMLs. Superenhancer clusters are shown to the right of the gray line. (B) Heatmap of H3K27ac counts across cell-specific and invariant enhancers. Each row represents a 2 kb window centered around the middle of top 600 GMP-specific, LSC-specific, mAML-specific, and invariant enhancers for H3K27ac. All reads were aligned to mm9. (C) Mean normalized LSC expression (x-axis) vs mean normalized GMP expression (y-axis) for genes associated with LSC-specific enhancers (red) or with GMP-specific enhancers (green). (D) Mean normalized LSC expression (x-axis) vs mean normalized mAML (y-axis) expression for genes associated with LSC-specific enhancers (red) or with mAML-specific enhancers (orange). (E,F) Colony formation assay at day 5 in LSCs infected with shRNAs targeting oncogenic and self-renewal genes. The number (E) and morphology (F) of CFUs for oncogenes and self-renewal genes shRNA-infected colonies is significantly different from the number and morphology of CFUs for controls (n = 3; mean ± SD). ∗P < .05; ∗∗P < .01. CFU, colony-forming units; SD, standard deviation.