Sleep programs the LSK epigenome and confers adaptability. (A) Experimental schematic. C, control. (B) Distribution of DA (Log₂FC > 2, P < 0.05, red circles) enhancer loci in control and SF LSKs. (C) Accessibility heatmap of DA enhancer loci between control and SF LSKs and corresponding accessibility in RS group, indicating preserved signature of loci not significantly different (Log₂FC < 2, P < 0.05) between SF and RS. (D) Kyoto Encyclopedia of Genes and Genomes pathway analysis of the retained signature. (E) Heatmap of enhancer loci associated with genes important to lymphocyte differentiation, myeloid differentiation, and cyclin signaling. For ATAC-seq analysis, n = 2 mice per group, repeated twice, for a total of n = 4 per group. (F and G) Representative peak map (F) and quantitative PCR analysis (G) of Cdkn1b, Cdkn2b, Cdkal1, Klf9, and Klf3 expression in LSKs of control, SF, and SF+RS mice (n = 4–7 mice per group). (H) Experimental set up, CLP. (I) Blood bacteremia and Ly6C^hi monocytes along with BM LSKs and proliferation 24 h after CLP. n = 4–8 mice per group. (J) Plasma cytokine levels. n = 8 mice per group. (K) Clinical score (n = 8 mice per group) and survival (n = 10 mice per group) after CLP. (L) Schematic of experimental design. (M and N) Blood monocyte numbers immediately prior to (M) and 24 h after (N) the CLP. n = 3–5 mice per group. (O) BM LSKs and proliferation 24 h after CLP. n = 5 mice per group. (P) Plasma cytokine levels and clinical score after CLP. n = 5 mice per group. Mean ± SEM. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.