Single-cell profiling quantifies the dose gap between population-average and complete pY-STAT1/3 suppression by JAK inhibitors

In two human monocytic cell lines, JAK inhibitors suppress IFN-γ– and IL-10–driven nuclear pY-STAT1/3 phosphorylation unevenly: at ≥80% mean inhibition, 76% (mean) vs 37% (log-mean) of cells remain above the non-stimulated range.

• Why it matters: Population-average potency can mask residual single-cell signaling, so it is unclear how much STAT1/3 activity persists when average suppression is strong.
• What they did: Nuclear STAT1 and STAT3 tyrosine phosphorylation were measured at single-cell resolution across 24 inhibitor profiles in IFN-γ– and IL-10–stimulated cells treated with six JAK-pathway inhibitors, comparing arithmetic-mean vs log10-transformed log-mean inhibition to partial and complete inhibition fractions.
• The result: Log-mean inhibition tracked partial-inhibition occupancy, while complete-inhibition occupancy required higher doses: median IC50 was 2.4-fold above log-mean IC50 and 7.4-fold above arithmetic-mean IC50, enabling estimation of cell fractions from standard inhibition curves.