Extended Data Fig. 4: TXNRD1 is required for cGAS-STING activation during therapy-induced senescence.
a, Immunoblot of the indicated proteins in cisplatin-induced senescent PEO1 cells with or without TXNRD1 knockdown. b-d, Representative images of immunostaining for cGAS and γH2AX in cisplatin-induced senescent PEO1 cells with or without TXNRD1 knockdown or treatment with Tri-1 or vehicle control (b). White arrows indicate examples of cGAS and γH2AX positive CCFs in control cells, while the yellow arrows indicate examples of cGAS negative, γH2AX positive CCFs in TXNRD1 knockdown or Tri-1 treated cells. γH2AX-positive CCFs that are positive for cGAS from senescent PEO1 cells with or without TXNRD1 knockdown were quantified (c). γH2AX-positive CCFs that are positive for cGAS from senescent PEO1 cells with or without TXNRD1 inhibitor Tri-1 treatment were quantified (d). Scale bar = 10 μm. e, f, Immunoblot of the indicated protein in control and cisplatin-induced senescent PEO1 cells with or without TXNRD1 knockdown or treatment with a pharmacological TXNRD1 inhibitor Tri-1 (5 μM) (e). In addition, cellular 2’ 3’-cGAMP levels were measured in the indicated cells (f). Data represent mean ± s.e.m. n = 3 biologically independent experiments. P-values were calculated using a two-tailed t test.
