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

被引：245

作者：

Bhaduri, Aparna ^{[1
,2
]}

Di Lullo, Elizabeth ^{[1
,2
]}

Jung, Diane ^{[1
,2
]}

Mueller, Soren ^{[1
,3
]}

Crouch, Elizabeth Erin ^{[4
]}

Espinosa, Carmen Sandoval ^{[1
,2
]}

Ozawa, Tomoko ^{[3
]}

Alvarado, Beatriz ^{[1
,2
]}

Spatazza, Julien ^{[2
,3
]}

Cadwell, Cathryn Rene ^{[5
]}

Wilkins, Grace ^{[1
,2
]}

Velmeshev, Dmitry ^{[1
,2
]}

Liu, Siyuan John ^{[2
,3
]}

Malatesta, Martina ^{[2
,3
]}

Andrews, Madeline Gail ^{[1
,2
]}

Mostajo-Radji, Mohammed Andres ^{[1
,2
]}

Huang, Eric Jinsheng ^{[5
]}

Nowakowski, Tomasz Jan ^{[1
,6
]}

Lim, Daniel Amos ^{[2
,3
]}

Diaz, Aaron ^{[1
,3
]}

Raleigh, David Ronan ^{[3
,7
]}

Kriegstein, Arnold Richard ^{[1
,2
]}

机构：

[1] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA

[4] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA

[5] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA

[6] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94158 USA

[7] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA

来源：

CELL STEM CELL | 2020年 / 26卷 / 01期

关键词：

SUBVENTRICULAR ZONE; BRAIN; EXPRESSION; INVASION; GLIOMAS; TRANSFORMATION; PROGENITORS; ORGANOIDS; NEURONS; MODELS;

D O I：

10.1016/j.stem.2019.11.015

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：48 / +

页数：22

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