Figure 6.

ELANE-Corrected HSPCs Restore Neutrophil Differentiation In Vivo

(A) FACS data showing the frequencies of human CD45⁺ cells (top) or CD33⁺CD15⁺CD66b⁺ mature neutrophils (Neu) (bottom) in the bone marrow (left) or spleen (right) of recipients at 20 weeks post-transplantation with non-repaired (ELANE-L172P) or repaired (ELANE-repair) HSPCs. (B) Absolute numbers of human CD45⁺ cells or neutrophils in the bone marrow (left) or spleen (right) of transplanted animals 20 weeks after reconstitution. Data are represented as mean ± SD for three mice. ∗p < 0.05 (two-tailed Mann-Whitney test). (C) Representative sequences of the ELANE WT, Mut, and repaired (Re) alleles in human mature neutrophils isolated from recipients 20 weeks after transplantation. The WT T nucleotide is indicated in red, the Mut C nucleotide in is indicated in blue, and silent mutations are indicated in magenta. (D) Pie chart summarizing the frequencies of the ELANE WT and repaired alleles in mature neutrophils. (E) Left: FACS data showing percentages of human CD33^hiCD15⁺ Promye and CD33^loCD15⁺ Neu in human CD45⁺ cells in the bone marrow of recipients 20 weeks after transplantation. Right: quantification for three mice; data are represented as mean ± SD. (F) Left: histograms showing annexin V⁺ apoptotic cells in human CD33^hiCD15⁺ promyelocytes from recipients 20 weeks after reconstitution. Right: quantification for three mice; data are represented as mean ± SD. See also Figures S7 and S8.