Figure S23. Functional importance of regulon activity during myeloid differentiation.

(A) UMAP embedding based on single-cell RNA-sequencing expression from wild-type (multiple cell types) and Irf8 KO (or Irf8−/−) single cells. (B) UMAP embedding based on regulon activity score from wild-type (multiple cell types) and Irf8 KO single cells. The regulon space captures cell type differences as with expression space. (C) Single-cell Irf8 expression in myeloid progenitors from wild-type (including monocytes and granulocytes) and Irf8 knockout cells (Purple). The Irf8 KO cells have a gradient expression of high and low cells. (D) Irf8 regulon activity in myeloid progenitors from wild-type (including monocytes and granulocytes) and Irf8 KO cells (Purple). Note: the Irf8 KO cells have diminished regulon activity score (compared with monocytes, consistent with change in their specification from monocyte to granulocytes). For calculating Irf8 regulon activity in both wild-type and Irf8 KO cells, we repeated AUCell 50 times and used the averaged activity score. (E) UpSet plot of Irf8 regulon composition in wild-type monocytes, wild-type granulocytes, and Irf8 KO cells. The Irf8 knockout cells alter and specify cell fate from monocytes to granulocytes, as highlighted by with drastically altered regulon composition in Irf8 KO cells.