Figure 5.
Single-cell RNA-seq of sorted CD34+CD45+cells from GATA2 WT vs GATA2+/−iPSC reveal subtle differences in lineage commitment and gene expression profiles of GATA2 target genes. Imputed cell type classification for single-cell RNA-seq data from healthy volunteer pair (WT vs GATA2+/−) (A) and GATA2 R337X pair (patient mutant vs corrected) (B). The gene expression data have been dimensionally reduced via Uniform Manifold Approximation and Projection. (C) Pseudotemporally ordered cells derived from iPSC of healthy volunteer. Cells are colored by cell type. The center of each subplot represents the branch point between the myeloid and lymphoid lineages; myeloid lineages move to the right as they mature and lymphoid lineages move to the left. (D) Pseudotemporal ordering of cells derived from GATA2 WT iPSC are colored in blue; those from GATA2+/− iPSC are colored in red. (E) Pseudotemporally ordered cells derived from iPSC of GATA2 R337X pair. (F) Pseudotemporal ordering of cells derived from a corrected clone of GATA2 R337X iPSC are colored in blue; those from GATA2 R337X iPSC are colored in red. (G) Fraction of each cell type per GATA2 status. (H) Volcano plot of differentially expressed genes depending on GATA2 status. The 2 dotted vertical lines indicate log2-fold change; 2 dotted horizontal lines indicate P < .05. Ba-Prog, basophil progenitor; DC-Prog, dendritic cell progenitor; Eo-Prog, eosinophil progenitor; Er-Pro, erythroid progenitor; Lymph-Prog, lymphoid progenitor; Mk-Er-Prog, megakaryocyte-erythrocyte progenitor; Mk-Prog, megakaryocyte progenitor; Mo-Prog, monocyte progenitor; MPP, multipotent progenitor; Neu-Prog, neutrophil progenitor.

Single-cell RNA-seq of sorted CD34+CD45+cells from GATA2 WT vs GATA2+/−iPSC reveal subtle differences in lineage commitment and gene expression profiles of GATA2 target genes. Imputed cell type classification for single-cell RNA-seq data from healthy volunteer pair (WT vs GATA2+/−) (A) and GATA2 R337X pair (patient mutant vs corrected) (B). The gene expression data have been dimensionally reduced via Uniform Manifold Approximation and Projection. (C) Pseudotemporally ordered cells derived from iPSC of healthy volunteer. Cells are colored by cell type. The center of each subplot represents the branch point between the myeloid and lymphoid lineages; myeloid lineages move to the right as they mature and lymphoid lineages move to the left. (D) Pseudotemporal ordering of cells derived from GATA2 WT iPSC are colored in blue; those from GATA2+/− iPSC are colored in red. (E) Pseudotemporally ordered cells derived from iPSC of GATA2 R337X pair. (F) Pseudotemporal ordering of cells derived from a corrected clone of GATA2 R337X iPSC are colored in blue; those from GATA2 R337X iPSC are colored in red. (G) Fraction of each cell type per GATA2 status. (H) Volcano plot of differentially expressed genes depending on GATA2 status. The 2 dotted vertical lines indicate log2-fold change; 2 dotted horizontal lines indicate P < .05. Ba-Prog, basophil progenitor; DC-Prog, dendritic cell progenitor; Eo-Prog, eosinophil progenitor; Er-Pro, erythroid progenitor; Lymph-Prog, lymphoid progenitor; Mk-Er-Prog, megakaryocyte-erythrocyte progenitor; Mk-Prog, megakaryocyte progenitor; Mo-Prog, monocyte progenitor; MPP, multipotent progenitor; Neu-Prog, neutrophil progenitor.

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