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. 2023 Jan 20;83(7):983–996. doi: 10.1158/0008-5472.CAN-22-2129

Figure 4.

Figure 4. Transient SWI/SNF inhibition depletes committed hematopoietic cells in BM but preserves HSC function. A, Total number of cells isolated from BM of BRM014- and vehicle-treated mice at day 14, N = 3 per condition. B, Quantification of accessible PU.1 motifs across specific BM cell types. M = monocytes, B = B cells, Kit+ = Kit+ progenitors, T = T cells, NK = NK cells. C, Cell-type-specific transcriptional profiles are unchanged by treatment, enabling consistent classification. UMAP embedding of individual cells pooled from all conditions. Resulting clusters are classified by immune cell type based on cell-specific expression profiles. D, Inferred total number of HSPC Kit+ and lineage committed Kit– cells determined by scRNA-seq. E, Flow cytometry quantification and histogram of lineage-committed (CD3, CD8, B220, GR1, TER119) and uncommitted CD45+ BM cells. F, Inferred total number of B cell and monocyte populations in BM determined by scRNA-seq. G, Total number of LSK (Lin–Sca-1+Kit+) HSPCs in BM by flow cytometry, N = 3 per condition. H, Competitive HSCT workflow and (I) representative flow plots of HSC engraftment and recapitulation of major hematopoietic lineages. N = 4 (vehicle), N = 6 (BRM014). Error bars: mean ± SEM.

Transient SWI/SNF inhibition depletes committed hematopoietic cells in BM but preserves HSC function. A, Total number of cells isolated from BM of BRM014- and vehicle-treated mice at day 14. N = 3 per condition. B, Quantification of accessible PU.1 motifs across specific BM cell types. M, monocytes; B, B cells; Kit+, Kit+ progenitors; T, T cells; NK, NK cells. C, Cell type–specific transcriptional markers were unchanged by treatment, enabling consistent classification. UMAP embedding of individual cells pooled from all conditions. Resulting clusters are classified by immune cell type based on cell-specific expression profiles. D, Inferred total number of HSPC Kit+ and lineage-committed Kit– cells determined by scRNA-seq. E, Flow cytometry quantification and histogram of lineage-committed (CD3, CD8, B220, GR1, TER119) and uncommitted CD45+ BM cells. F, Inferred total number of B cell and monocyte populations in BM determined by scRNA-seq. G, Total number of LSK (Lin–Sca-1+Kit+) HSPCs in BM by flow cytometry. N = 3 per condition. H and I, Competitive HSCT workflow (H) and representative flow plots (I) of HSC engraftment and recapitulation of major hematopoietic lineages. N = 4, vehicle; N = 6, BRM014. Error bars, mean ± SEM. n.s., nonsignificant.