Overexpanded myeloid-biased Tet2 KO clones exhibit significantly reduced expression of genes associated with RNA splicing and AML. (A) Workflow to connect clonal tracking data to single-cell gene expression profiles. (B) Uniform manifold approximation and projection (UMAP) visualization of myeloid-biased HSCs. (C) Differentially expressed genes comparing overly expanded and normally expanded HSCs that are myeloid-biased and Tet2 KO. The complete gene list is available in supplemental Table 2. (D) Examples of significantly differentially expressed genes are highlighted in red font in panel C. (E) UMAP visualization of myeloid-biased MPP3s. (B,E) Colors highlight cells identified as derived from myeloid-biased clones. The rest of the cells are shown in gray. (F) Differentially expressed genes comparing overly expanded and normally expanded MPP3s that are myeloid-biased and Tet2 KO. The complete gene list is available in supplemental Table 2. (G) Examples of significantly differentially expressed genes are highlighted in red font in (F). (D,G) One-side Mann-Whitney U test. The adjusted P values (Benjamini–Hochberg correction) are shown. (H,I) Gene ontology (GO) analysis of significantly differentially expressed genes (adjusted P < .1) from panels C and F. All the GO terms associated with biological processes (H) and diseases (I) shared by the GO analysis of HSC and MPP3 data are shown. The complete GO list is available in supplemental Table 2. (J) Comparing averaged expression of all genes associated with the mRNA metabolic process GO terms (GO:0016071) and AML (C0026998). Two-tailed Mann-Whitney U test. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001.