Extended Data Fig. 9: Hematopoietic stem cell (HSC) trajectory and vector field analysis, and transcription factor (TF) knockout and overexpression analysis.

a, UMAP of HSCs with supervised pseudotime trajectory from cluster C6 (HC enriched) to cluster C7 (sepsis but not SRS1 enriched). b, STAT3 and CEBPB gene expression with pseudotime. c, Genes (left) and TF motifs (right) which change along C6⁻C7 pseudotime trajectory and correlate with each other (Pearson’s r > 0.5, FDR < 0.05). d, CEBPA gene expression with pseudotime. e, CellOracle⁶⁸ in silico knockout (top) and overexpression (bottom) of CEBPA and CEBPB and effects on clusters C5/6/7, with arrows displaying predicted changes in cell fate after gene of interest is perturbed (Methods). f–i, HSC clusters C5/6/7 vector field analysis with dynamo⁷⁰. f, UMAP of HSC clusters C5/6/7 with RNA velocity stream directions plotted. g, RNA velocity based pseudotime of HSC clusters C5/6/7. h, dynamo acceleration and curvature vector fields. i, In silico knockout of CEBPA (left), CEBPB (middle) and STAT3 (right) and effects on clusters C5/6/7 with arrows displaying predicted changes in cell fate after gene of interest is perturbed. j, dynamo Jacobian analysis of gene-gene regulatory relationships. Scatter-plots show normalized expression values of genes of interest along x and y axes. Blue denotes inhibition of the numerator gene by the denominator gene in the Jacobian partial derivative, while red denotes activation of the numerator by the denominator.