Outer Radial Glia-like Cancer Stem Cells Contribute to Heterogeneity of Glioblastoma.,Cell Stem Cell

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Outer Radial Glia-like Cancer Stem Cells Contribute to Heterogeneity of Glioblastoma.
Cell Stem Cell ( IF 23.9 ) Pub Date : 2020-01-02 , DOI: 10.1016/j.stem.2019.11.015
Aparna Bhaduri ₁ , Elizabeth Di Lullo ₁ , Diane Jung ₁ , Sören Müller ₂ , Elizabeth Erin Crouch ₃ , Carmen Sandoval Espinosa ₁ , Tomoko Ozawa ₄ , Beatriz Alvarado ₁ , Julien Spatazza ₅ , Cathryn René Cadwell ₆ , Grace Wilkins ₁ , Dmitry Velmeshev ₁ , Siyuan John Liu ₅ , Martina Malatesta ₅ , Madeline Gail Andrews ₁ , Mohammed Andres Mostajo-Radji ₁ , Eric Jinsheng Huang ₆ , Tomasz Jan Nowakowski ₇ , Daniel Amos Lim ₅ , Aaron Diaz ₂ , David Ronan Raleigh ₈ , Arnold Richard Kriegstein ₁

Affiliation

Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA.
Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA.
Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA 94143, USA.

Glioblastoma is a devastating form of brain cancer. To identify aspects of tumor heterogeneity that may illuminate drivers of tumor invasion, we created a glioblastoma tumor cell atlas with single-cell transcriptomics of cancer cells mapped onto a reference framework of the developing and adult human brain. We find that multiple GSC subtypes exist within a single tumor. Within these GSCs, we identify an invasive cell population similar to outer radial glia (oRG), a fetal cell type that expands the stem cell niche in normal human cortex. Using live time-lapse imaging of primary resected tumors, we discover that tumor-derived oRG-like cells undergo characteristic mitotic somal translocation behavior previously only observed in human development, suggesting a reactivation of developmental programs. In addition, we show that PTPRZ1 mediates both mitotic somal translocation and glioblastoma tumor invasion. These data suggest that the presence of heterogeneous GSCs may underlie glioblastoma's rapid progression and invasion.

中文翻译：

外放射状胶质细胞样癌症干细胞导致胶质母细胞瘤的异质性。

胶质母细胞瘤是一种毁灭性的脑癌。为了确定可能阐明肿瘤侵袭驱动因素的肿瘤异质性方面，我们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映射到发育中和成人大脑的参考框架上。我们发现单个肿瘤内存在多个 GSC 亚型。在这些 GSC 中，我们发现了一个类似于外放射状神经胶质细胞 (oRG) 的侵入性细胞群，这是一种胎儿细胞类型，可扩大正常人类皮层中的干细胞生态位。使用原发性切除肿瘤的实时延时成像，我们发现肿瘤衍生的 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体细胞易位行为，表明发育程序重新激活。此外，我们显示 PTPRZ1 介导有丝分裂体细胞易位和胶质母细胞瘤肿瘤侵袭。这些数据表明，异质性 GSC 的存在可能是胶质母细胞瘤快速进展和侵袭的基础。

更新日期：2020-01-02

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