NPAS3 and neoplasm: In contrast, the Constructive GSC state relies on transcription factors including OLIG2, a known GSC marker (Trépant et al., 2015); AHR involved in tumor microenvironment responses and metabolic adaptation (Gabriely et al., 2017); NPAS3, a regulator of Notch signaling and neurogenesis (Michaelson et al., 2017); and ASCL1, a critical regulator of GSC differentiation and marker of sensitivity to Notch inhibition in GSCs (Park et al., 2017; Rajakulendran et al., 2019).