LNK inhibition increases CB HSC reconstitution of all hematopoietic lineages in the bone marrow and spleen. CB-derived CD34⁺ HSPCs were transduced with lentiviral shRNAs to Luc or LNK and transplanted into NBSGW mice as described in Figure 1. After 16 to 27 weeks, BMs and spleens from the recipient mice were analyzed for human cell engraftment. (A) Mean percent mCherry⁺ in hCD45⁺ BM and spleen cells. (B) Representative myeloid and lymphoid flow cytometric plots in xenotransplanted mice. T cells (T) = CD3⁺, B cells (B) = CD19⁺, granulocytes (Gran) = CD33⁺SSC^hi, and monocytes (Mono) = CD33⁺SSC^lo. (C) Representative erythroid and megakaryocyte flow cytometric plots in xenotransplanted mice. Erythroid progenitors (Ery) = hCD45⁺CD235a⁺, red blood cells (hRBC) = hCD45^-CD235a⁺, and megakaryocytes (Mk) = hCD45⁺CD41a⁺. (D) Mean percent mCherry⁺ within each hematopoietic lineage of the engrafted hCD45⁺ cells in the BM as shown in panels B and C. (E) Lineage distribution of engrafted hCD45⁺mCherry⁺ cells in the BM. (F) Mean percent mCherry⁺ of hRBCs in the BM as shown in panel C. (G) Representative platelet flow cytometric plot for panel H. (H) Mean percent mCherry⁺ of human platelets (hPlts) (FSC^lohCD45⁻mCD45⁻hCD61⁺) in the BM. In all relevant panels, each symbol represents an individual mouse; bars indicate mean values; error bars indicate plus or minus SEM. *P < .05; **P < .01; ***P < .001 as determined by 1- (panels F and H) or 2-way (panels A, D, and E) ANOVA followed by Dunnett’s multiple comparisons to shLuc. N = 23 shLuc, n = 9 shLNK #1, n = 7 shLNK #2, and n = 8 shLNK #3 transplanted mice. The data are pooled from biological replicates n = 8 CBs for shLuc, 3 for shLNK #1, 2 for shLNK #2, and 3 for shLNK #3.