Extended Data Fig. 5: Role of PARP1 in differentiating macrophages.
a-h, CD14+ cells from healthy human donors were isolated and differentiated to mature myeloid cells for 5 days with IL-4 and GM-CSF in presence or absence of the PARP inhibitors: Olaparib, Niraparib, and Talazoparib, and then collected for immunophenotyping by flow cytometry. a,b, PARP inhibitor treatment did not affect the viability (a) or proportion of CD45+ cells (b). PARP inhibitors decreased the proportion of CD14+ (c) and CD163+ (d) cells and increased the proportion of CD80+ (e), pTBK1+ (f), PD-L1+ (g) and CSF-1R+ (h) macrophages. Statistical analyses were performed using unpaired one-tailed t-test: Error bars represent standard error of mean (±SEM) with n = 5 healthy human donors per group. Exact p values indicated in each panel for each comparison. i-o, Bone marrow from wild-type (wt) and parp1-/- mice was isolated and differentiated to mature myeloid cells for 5 days with IL-4 plus GM-CSF in the presence or absence of Olaparib, then collected for immunophenotyping by flow cytometry. i, Olaparib did not affect the viability of differentiated macrophages. Olaparib increased the differentiation to mature myeloid cells (j), and macrophages (k), and increased PD-L1 expression on macrophages (l), independent of PARP1 status. However, Olaparib-induced expression of CSF-1R on macrophages (m) and increased expression of pTBK1 on myeloid cells (n) and macrophages (o) was PARP1-dependent. Statistical analyses were performed using one-way ANOVA with uncorrected Fisher’s LSD. Error bars represent standard error of the mean (±SEM) with n = 5 mice per group. Exact p values indicated in each panel for each comparison.
