Activated KRAS reprograms neural progenitor cells to glioma stem cell‑like phenotype
浏览次数:32 分享:
Glioma is the most common primary brain tumor. Glioma stem cells (GSCs) are the origin of gliomagenesis and may develop from normal neural progenitor cells (NPCs). However, how neoplastic transformation occurs in normal NPCs and the role of the Ras/Raf/MAPK pathway in NPC transformation is unclear. The present study generated NPCs from human embryonic stem cells (ESCs) carrying gene alterations in the Ras/Raf/MAPK pathway. The CCK‑8 proliferation, single‑cell clonal expansion, cell migration, RT‑qPCR, immunofluorescence staining, western blotting, transcriptome and Seahorse analyses, and intracranial implantation assay were performed to identify the characterization of transformed NPCs in vitro and in vivo. Brain organoids were used to verify the phenotypes transforming in NPCs. KRAS‑activated NPCs exhibited increased proliferation and migration in vitro. KRAS‑activated NPCs showed atypical morphology and formed aggressive tumors in immunodeficient mice. At the molecular level, KRAS‑activated NPCs displayed neoplasm‑associated metabolic and gene expression profiles. Moreover, activation of KRAS led to substantial cell proliferation and abnormal structure in ESC‑derived brain organoids. The present study showed that activated KRAS transformed normal NPCs to GSC‑like cells and established a simple cellular model to investigate gliomagenesis.Keywords: KRAS; cell transformation; glioma stem cell; gliomagenesis; neural progenitor cell.
详见LabEx网站( www.u-labex.com)或来电咨询!
基因水平:PCR Array、RT-PCR、PCR、单细胞测序
蛋白水平:MSD、Luminex、CBA、Elispot、Antibody Array、ELISA、Sengenics
细胞水平:细胞染色、细胞分选、细胞培养、细胞功能
组织水平:空间多组学、多重荧光免疫组化、免疫组化、免疫荧光
数据分析:流式数据分析、组化数据分析、多因子数据分析
联系电话:4001619919
联系邮箱:labex-mkt@u-labex.com
公众平台:蛋白检测服务专家