Given that transition of GSCs to ECs occurred in the hypoxic microenvironment (49, 50) and the upregulated expression of P4HA1 and COL6A1 under hypoxia (11, 51), combined with our experimental results, there might exist a PH4A1/COL6A1 regulation axis as an adaptive response to the hypoxic microenvironment, cooperating with the ECM to drive GSCs to differentiate into ECs and subsequently promote neovascularization in GBM (Figure 8). The gene discussed is P4HA1; the disease is glioblastoma.