The integration of co-expression networks reveals MYB as a pivotal driver of monocyte differentiation. (A) Pairing of positive and negative co-expression networks at time points 24 h and also at 96 h reveals MYB as a pivotal driver (red arrow), hingeing two antagonistic network modules. (B) siRNA mediated knockdown of MYB in THP-1 cells leads to cellular differentiation observed by cell adherence to the dish after several washing steps. (C) Depletion of MYB in THP-1 cells induces expression of key pro-differentiation factors such as EGR2, MAFB, and PPARG as compared to siRNA control. (D) MYB knockdown followed by single-cell gene expression analysis reveals various modes of gene expression regulation and distribution (grey line = control (n = 43), brown line = MYB siRNA knockdown (n = 43), red bar = detection threshold at 5). Scale bar = 50 μm.