术后残存于瘤腔边缘的胶质母细胞瘤（GBM）干细胞是导致复发的根源，TGFβ是诱导GBM细胞获得干性的重要因子，但GBM中高表达、自分泌TGFβ的机制仍待阐明。我们前期从GBM瘤心、瘤周分离了多对肿瘤细胞，转录组学及实验发现：GBM瘤周细胞高表达TGFβ、TGFβ受体、OLFM2，且更容易发生干细胞转变；进一步实验发现：TGFβ1/2可促进OLFM2入核，OLFM2可结合转录因子SRF；转运蛋白KPNA2预测可结合OLFM2，SRF预测可结合TGF1/2启动子区。本研究将运用双光子成像、Crispr/Cas9等技术，在体内、体外验证：TGFβ/SMADs/KPNA2促进OLFM2表达及入核，OLFM2入核后结合SRF并作用于TGFβ启动子区，促进GBM细胞高表达、自分泌TGFβ，并获得干细胞特性。本项目将揭示OLFM2在GBM细胞获得干性、导致复发中的关键作用，为GBM的治疗提供候选靶点。

The remaining stem cells existed in the resection margin of glioblastoma(GBM) are the origin of tumor recurrence, transforming growth factor-β(TGF-β) is one of the most important cytokines induced stemness of GBM cells. However, the mechanism of TGF-β highly express and autocrine in GBM still remains unclear. Previously, we have cultured several paired of primary GBM cells isolated from tumor core and peritumoral region. Through transcriptomics analyses and verification of cell experiments, we have found that the expression of TGF-β, TGF-β receptor and OLFM2 were up-regulated in peritomoral GBM cells, and these cells were easier to gain stem cell characteristics. Through further experiments we have confirmed that both TGF-β1 and TGF-β2 could induce the nucleus translocation of OLFM2, and OLFM2 could bond with SRF (serum responding factor) which is a transcription factor. Further, OLFM2 is predicted to bond with transport protein KPNA2 and SRF is predicted to bond with the promoter region of TGF-β1/2 promotor region after bioinformatic analyses. In this research, using advanced methods such as Crispr/Cas9 and two-photon imaging, in vivo and vitro, we will confirm that TGFβ/SMADs/KPNA2 axis promote the expression and nucleus translocation of OLFM2, a complex formed with transcription factor SRF and OLFM2 which act as a co-activate factor could bond with TGF-β1/2 promotor region and promote the expression and autocrine of TGF-β1/2 in GBM cells, the TGF-β1/2 autocrine loop result in the stem cell transformation of GBM cells and lead to the tumor recurrence finally. We will reveal the key role OLFM2 played in GBM stem cell transformation and tumor recurrence, and provide molecular oncotarget of GBM therapy.