Kinase-inactivated CDK6 enhances HSC homing and self-renewal. (A) Top upregulated genes in dormant Cdk6^KM/KM HSCs compared with Cdk6^+/+ and Cdk6^–/– cells from scRNA-seq. (B) Schematic representation of BM homing assay in vivo. (C) Flow cytometry analysis of homed CD45.2⁺Cdk6^+/+, Cdk6^–/–, and Cdk6^KM/KM LSK and HSC/MPP1 of LSK cells 18 hours after injection into CD45.1⁺ recipients (n ≥ 11 recipients and donors, mean ± SEM). (D) Serial BM transplantation workflow of Cdk6^+/+, Cdk6^–/–, and Cdk6^KM/KM BM cells. (E) Representative flow cytometry plots of gated LSK cells over 4 rounds of transplantation (TP). (F-G) Percentage of engrafted CD45.2⁺Cdk6^+/+, Cdk6^–/–, and Cdk6^KM/KM LSK and HSC/MPP1 cells over 4 rounds of transplantation. (H) Lineage distribution of engrafted CD45.2⁺Cdk6^+/+, Cdk6^–/–, and Cdk6^KM/KM BM cells (n = 3-6/genotype, mean ± SEM). (I) Experimental-design competitive BM transplantation assay, depicting a 1:1 ratio transplantation of CD45.1⁺Cdk6^+/+ together with either CD45.2⁺Cdk6^+/+ or Cdk6^KM/KM BM into lethally irradiated recipient mice. (J) End point analysis of competitive transplantation showing CD45.2⁺Cdk6^+/+ and Cdk6^KM/KM HSC/MPP1 cells (n = 7 per group, mean ± SEM). ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001.