Fig. 3: ERRα/PGC-1α-dependent GD3 expression is absent in OIS allowing their activation of NK cells.
a, qPCR assessment of ST8SIA1, CDKN2A and CDKN1A expression in MRC5 cells in tamoxifen (tam)-inducible hRAS senescence. b,c, Senescence-related GSEA on SenMayo (b) and SASP (c) gene sets of hRAS-induced senescent MRC5 cells. d, Quantification of the NK cell infiltration induced by proliferative, replicative senescent, oncogene-induced or stress-induced MRC5 cells in Matrigel plug assay. e, Quantification of mouse NK cell degranulation in in vitro co-culture experiment with oncogene-induced or bleomycin-induced senescence in hMECs. f,e, Quantification of the in vivo NK cell degranulation induced by young, replicative, oncogene-induced or stress-induced senescent MRC5 cells in Matrigel plug assay. g,h, IPA of ST8SIA1 upstream pathways. Gene networks revealed by DEG in replicative senescence (g) and hRAS oncogene-induced senescence (h) in MRC5 cells compared to their control by RNA-seq (Extended Data Fig. 1) are overlayed in colors on each network. i,j, Flow cytometry assessment of GD3 expression (i) and qPCR assessment (j) of ST8SIA1 expression by replicative senescent MRC5 cells after 72 h of treatment with PGC1-α inhibitor (SR18292) and ERRα inhibitor (XCT790) normalized on DMSO-treated cells. k–n, qPCR analysis of ST8SIA1 (k), PPARGC1A (l) and ESRRA (m) normalized on proliferative MRC5 cells and ratio between the expressions of PPARGC1A and ESRRA (n). o,p, qPCR analysis of NRIP1 normalized on proliferative MRC5 cells (o) and ratio between the expressions of PPARGC1A and NRIP1 (p). q, Representative scheme of the regulation of ST8SIA1 expression by the nuclear receptor ERRα, its co-activator PGC1-α and its co-repressor RIP140. Data are represented as mean ± s.e.m. (a). Experiments in a and k–p were performed on n = 3 batches of SnCs. Experiments in i and j were performed on n = 4 independent experiments. Experiments in d and f are representative of n = 9 mice. Experiment in e was performed on n = 10 independent experiments. *P < 0.05, **P < 0.01 and ***P < 0.001; two-tailed Mann–Whitney U-test.
