Fig 1. Hematopoietic specific loss of Stag2, but not Stag1, results in altered stem cell function.
A) Stag2 KO, but not Stag1 KO mice have increased LSK (Lin−Kit+Sca1+) hematopoietic stem cells (Log2FC=2.2; p<0.01) B) Whole bone marrow plated in cytokine-enriched methylcellulose. Stag2 KO marrow, but not WT and Stag1 KO, has increased self-renewal capacity and can serially replate (>7 platings). Competitive bone marrow transplantation of C) Stag2 WT (Red)/KO (Blue) or D) Stag1 WT (Green)/KO (Purple) bone marrow mixed 1:1 with Cd45.1 normal marrow. Stag2 KO shows increased chimerism in stem and progenitor populations in the bone marrow at 16 weeks. E) Kaplan-Meier curve shows Stag2−/y/Stag1−/− is lethal with a median survival of 0.7 weeks (p=0.01). Stag2−/y/Stag1−/+ has a lethal phenotype with a median survival of 27.7 weeks (p=0.05). F) Hematoxylin and eosin (H&E) staining of Stag2/Stag1 KO bone marrow reveals marked aplasia. G) Left: t-SNE projection of library-size normalized and log transformed data for inferred HSC subset (2025 cells). Each dot represents a single cell colored by genetic condition (Stag2 KO (shades of blue), Stag2 WT (shades of red). Middle: t-SNE projection colored by the second and third principal components most correlated with lymphoid priming and cell cycle, respectively. Right: Distribution of cells along lymphoid and cell cycle components; p-values for Mann-Whitney U test are shown.