Kälin Roland E, Cai Linzhi, Li Yuping, Zhao Dongxu, Zhang Huabin, Cheng Jiying, Zhang Wenlong, Wu Yingxi, Eisenhut Katharina, Janssen Philipp, Schmitt Lukas, Enard Wolfgang, Michels Friederike, Flüh Charlotte, Hou Mengzhuo, Kirchleitner Sabrina V, Siller Sebastian, Schiemann Matthias, Andrä Immanuel, Montanez Eloi, Giachino Claudio, Taylor Verdon, Synowitz Michael, Tonn Jörg-Christian, von Baumgarten Louisa, Schulz Christian, Hellmann Ines, Glass Rainer
Neurosurgical Research, University Hospital, LMU Munich, 81377 Munich, Germany; Walter-Brendel-Centre of Experimental Medicine, University Hospital, LMU Munich, 81377 Munich, Germany.
Walter-Brendel-Centre of Experimental Medicine, University Hospital, LMU Munich, 81377 Munich, Germany; Department of Neurology, University Hospital, LMU Munich, 81377 Munich, Germany.
Cell Syst. 2021 Mar 17;12(3):248-262.e7. doi: 10.1016/j.cels.2021.01.002. Epub 2021 Feb 15.
Aggressive brain tumors like glioblastoma depend on support by their local environment and subsets of tumor parenchymal cells may promote specific phases of disease progression. We investigated the glioblastoma microenvironment with transgenic lineage-tracing models, intravital imaging, single-cell transcriptomics, immunofluorescence analysis as well as histopathology and characterized a previously unacknowledged population of tumor-associated cells with a myeloid-like expression profile (TAMEP) that transiently appeared during glioblastoma growth. TAMEP of mice and humans were identified with specific markers. Notably, TAMEP did not derive from microglia or peripheral monocytes but were generated by a fraction of CNS-resident, SOX2-positive progenitors. Abrogation of this progenitor cell population, by conditional Sox2-knockout, drastically reduced glioblastoma vascularization and size. Hence, TAMEP emerge as a tumor parenchymal component with a strong impact on glioblastoma progression.
像胶质母细胞瘤这样的侵袭性脑肿瘤依赖于其局部环境的支持，肿瘤实质细胞亚群可能促进疾病进展的特定阶段。我们使用转基因谱系追踪模型、活体成像、单细胞转录组学、免疫荧光分析以及组织病理学研究了胶质母细胞瘤微环境，并鉴定出一群以前未被认识的具有髓样样表达谱的肿瘤相关细胞（TAMEP），它们在胶质母细胞瘤生长过程中短暂出现。通过特定标记物鉴定了小鼠和人类的TAMEP。值得注意的是，TAMEP并非源自小胶质细胞或外周单核细胞，而是由一部分中枢神经系统驻留的、SOX2阳性祖细胞产生。通过条件性Sox2基因敲除消除这一祖细胞群体，可显著减少胶质母细胞瘤的血管生成和大小。因此，TAMEP作为肿瘤实质成分出现，对胶质母细胞瘤进展有强烈影响。
