Fig. 4

Gene expression noise increases during hematopoietic differentiation. a UMAP representation of hematopoietic stem and progenitor cells from the bone marrow of wildtype (WT) mice [34]. Major cell populations and VarID2 transition probabilities (“Methods”) between clusters are highlighted. b Quantification of cellular noise (average \(\varepsilon\) across all genes per cell) across clusters from the WT dataset in a. Horizontal line corresponds to the median noise level of the LT-HSC population. Boxes indicate inter-quartile range (IQR), and whiskers correspond to ±1.5*IQR of the box limits. Outliers beyond the whisker limits are depicted. Vertical axis limits are manually adjusted for better visualization. c UMAP representation of a hematopoietic stem and progenitor cells from Kit W⁴¹/W⁴¹ mutant mice [34]. d As b, but showing cellular noise estimates of the W⁴¹/W⁴¹ dataset in c. e Differentially noisy genes identified between the LT-HSC populations of W⁴¹/W⁴¹ versus WT mice. MA plot shows log₂FC of noise on the y-axis, and average expression on the x-axis. Threshold values: log₂FC > 1, padj < 0.001. f Pathway enrichment analysis of the genes with increased noise in W⁴¹/W⁴¹ mice from e. g Noise \(\varepsilon\) estimates of genes involved in DNA replication. Quantities from each dataset were separated into LT-HSCs and the remaining cells, denoted as MPP. LT-HSC, long-term hematopoietic stem cells; MPP, multipotent progenitors; Ly, lymphocytic; My, myelocytic; Mo, monocytic; GN, granulocytic neutrophil; Ba, basophylic; MC, mast cells; Mk, megakaryocytic; Ery, erythroid; Div; dividing cells