Figure 5.

High GATA-1 protein abundance delineates epigenetic program for erythroid commitment in RBC developmental trajectory

(A) BM aspirate is ficolled and enriched for CD34⁺ cells before gating for CD123^– MEP population (CD34⁺/CD38⁺/CD10^–/CD45RA^–/CD123^–) and selecting high- (25%–40%) and mid- (∼lower 30%) GATA-1-expressing cells within each compartment.

(B) GATA-1-high cells from CD34⁺/CD38⁺ and CD123^– MEP compartments InTAC-seq data were simulated as scATAC counts and projected on scATAC UMAP space.

(C) Putative erythropoiesis trajectory constructed from HSCs to late erythoid populations and overlaid on scATAC UMAP.

(D) Heatmap of top variable TFs by ChromVAR deviation scores across constructed erythroid trajectory with the projected position of GATA-1-high InTAC-seq samples indicated in red as the point of GATA-1-high overlap, in blue as the before point, and in green as the after point. Top: line plot of InTAC-seq-denoted GATA-1-high-simulated scATAC cells as binned across pseudotime.

(E) Top 20 genes significantly enriched (of fold change 2 and above) in integrated scRNA-seq data between the 3 bins, before, at, and after GATA-1-high overlap points in trajectory.

(F) Summary schematic of continuous differentiation to erythrocytes in BM with downregulation of lymphoid/myeloid TF activity and gene expression programs and upregulation of erythroid TF activity and gene expression programs. High GATA-1 protein abundance overlaps epigenetic program shift to erythroid lineage commitment in human BM.