美国加州大学旧金山分校Arnold Richard Kriegstein、David Ronan Raleigh等研究人员合作发现，外放射状神经胶质样干细胞（GSC）促进成胶质母细胞瘤的异质性。这一研究成果于2020年1月2日发表在国际学术期刊《细胞—干细胞》上。

为了确定可能阐明肿瘤侵袭驱动因素的肿瘤异质性，研究人员创建了胶质母细胞瘤肿瘤细胞图谱，其中癌细胞的单细胞转录组学被映射到发育中和成年人脑的参考框架上。研究人员发现单个肿瘤内存在多个GSC亚型。在这些GSC中，研究人员确定了一种与外放射状神经胶质（oRG）类似的侵袭性细胞群，这是一种胎儿细胞类型，可在正常人的皮质中扩展干细胞的微环境。使用原发性切除肿瘤的实时延时成像，研究人员发现肿瘤来源的oRG样细胞经历了以前仅在人类发育中观察到的特征性有丝分裂染色体移位行为，这提示了发育程序的重新激活。此外，研究人员显示PTPRZ1介导有丝分裂的染色体易位和胶质母细胞瘤肿瘤侵袭。这些数据表明，异种GSC的存在可能是胶质母细胞瘤快速进展和侵袭的基础。

据介绍，胶质母细胞瘤是脑癌的恶性形式。

附：英文原文

Title: Outer Radial Glia-like Cancer Stem Cells Contribute to Heterogeneity of Glioblastoma

Author: Aparna Bhaduri, Elizabeth Di Lullo, Diane Jung, Sren Müller, Elizabeth Erin Crouch, Carmen Sandoval Espinosa, Tomoko Ozawa, Beatriz Alvarado, Julien Spatazza, Cathryn René Cadwell, Grace Wilkins, Dmitry Velmeshev, Siyuan John Liu, Martina Malatesta, Madeline Gail Andrews, Mohammed Andres Mostajo-Radji, Eric Jinsheng Huang, Tomasz Jan Nowakowski, Daniel Amos Lim, Aaron Diaz, David Ronan Raleigh, Arnold Richard Kriegstein

Issue&Volume: 2020/01/02

Abstract: Glioblastoma is a devastating form of brain cancer. To identify aspects of tumor heterogeneitythat may illuminate drivers of tumor invasion, we created a glioblastoma tumor cellatlas with single-cell transcriptomics of cancer cells mapped onto a reference frameworkof the developing and adult human brain. We find that multiple GSC subtypes existwithin a single tumor. Within these GSCs, we identify an invasive cell populationsimilar to outer radial glia (oRG), a fetal cell type that expands the stem cell nichein normal human cortex. Using live time-lapse imaging of primary resected tumors,we discover that tumor-derived oRG-like cells undergo characteristic mitotic somaltranslocation behavior previously only observed in human development, suggesting a reactivationof developmental programs. In addition, we show that PTPRZ1 mediates both mitoticsomal translocation and glioblastoma tumor invasion. These data suggest that the presenceof heterogeneous GSCs may underlie glioblastoma’s rapid progression and invasion.

DOI: 10.1016/j.stem.2019.11.015

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30470-9