The hypoxia-dependent regulation of GPR133 expression suggests that signaling mediated by GPR133 could be critical for self-renewal of CD133+ GSCs, which reside in hypoxic microenvironments of GBM.11 To test this hypothesis, we used lentiviral shRNA-mediated knockdown of GPR133 in GBML20 and GBML8 (Figure 4 and Supplementary Figure 6, respectively). Here, ADGRD1 is linked to glioblastoma.