Heterozygous ITPR3 variants primarily cause a hematopoietic defect correctable via HCT. (A) Graphs showing percentage of PBMCs undergoing apoptosis (AnnexinV⁺7AAD⁻) in patients (P2: two to three independent replicates; P4: one replicate) versus HDs at (I) baseline, representing apoptosis determined on day 0 in unstimulated PBMCs; this is shown alongside (II) fold change in percentage apoptotic cells in stimulated versus unstimulated PBMCs after culture with anti-CD3 and IL-2 for 6–7 days, followed by stimulation with PHA or anti-FAS IgM. Bars represent the media and lines the interquartile range; results are not statistically significant via multiple unpaired t tests with Holm–Sidak correction for multiple comparisons. (B and C) Flow cytometry plots showing proportions (within live CD45⁺ cells) of CD4⁻CD8⁻ double negative (DN) T cells, CD4⁺CD8⁺ DP T cells, CD3⁺TCRαβ⁺, and CD3⁺TCRγδ⁺ T cells (B) after 6 wk of ex vivo T cell differentiation of CD34⁺ cells isolated from P2 (bone marrow) and from one HD (cord blood) in a two-dimensional (2D) co-culture with OP9/DL1 stromal cells, and (C) after 6 wk of differentiation of CD34⁺ cells isolated from P5 (bone marrow) and from one HD (cord blood) in a three-dimensional (3D) co-culture with MS5/DL1 stromal cells in ATOs. All co-cultures were set up with at least three replicates in each experiment. (D) Distribution of maturation-associated T cells subsets displayed in stacked bar charts for CD4⁺ (left) and CD8⁺ T -cells (right) in P1, P2, P3, and P5 post-HCT at last follow-up versus adult (Ad.) and pediatric (Ped.) HDs; HD data has been combined and mean and standard deviation (error bars) are plotted. (E–G) Representative flow cytometry plots showing recovery of (E) Treg, (F) NKT, and (G) γδ T cells in patients post-HCT; representative of two to three independent experiments.