Figure 5. Single-cell ATAC-seq reveals shifts in motif accessibility.

a) Uniform Manifold Approximation and Projection (UMAP) for snATAC-seq data (n = 20,029 cells). HSC = hematopoietic stem cell; MEP = megakaryocyte-erythrocyte progenitor; MPP = multi-potent progenitor; IMP = immature myeloid progenitor; CLP = common lymphoid progenitor; LMPP = lymphoid-primed multi-potent progenitor; CMP = common myeloid progenitor. b) Single cell scores for available bulk ATAC-seq profiles from the ImmGen Database⁶¹ of FACS-sorted hematopoietic progenitors (see online methods). c) Single cell motif accessibility deviation scores as a proxy of transcription factor binding activity⁶² for Tal1 and Spi1 transcription factors for WT (n = 5,810 cells), for each of the defined clusters as calculated by chromVar⁶³ for the DNA binding motifs available from the HOCOMOCO v11 database⁴⁶. d) Motif accessibility correlation between single cells. Mean accessibility for each transcription factor was calculated using chromVar⁶³, followed by cell-to-cell Pearson correlation of motif accessibility calculated for WT cells from the HSC cluster (n = 1,410 cells) e) Motif accessibility deviation scores comparison between WT (n = 1,410 cells), Tet2 KO (n = 1,173) and Dnmt3a KO (n = 1,305 cells) cells mapped to the HSC cluster (two-sided Wilcoxon rank sum test). f) Mean CpG frequency per base of de novo motifs divided into quartiles based on the CpG content for Tet2 KO (n = 27 motifs) or Dnmt3a KO (n = 27 motifs).