Spatial transcriptomics reveals niche-specific enrichment and vulnerabilities of radial glial stem-like cells in malignant gliomas.
Spatial transcriptomics reveals niche-specific enrichment and vulnerabilities of radial glial stem-like cells in malignant gliomas.
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DOI：
10.1038/s41467-023-36707-6
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发表时间：
2023-02-23
影响因子：
16.6
通讯作者：
Wang, Yuan
中科院分区：
文献类型：
--
作者：
Ren, Yanming;Huang, Zongyao;Zhou, Lingling;Xiao, Peng;Song, Junwei;He, Ping;Xie, Chuanxing;Zhou, Ran;Li, Menghan;Dong, Xiangqun;Mao, Qing;You, Chao;Xu, Jianguo;Liu, Yanhui;Lan, Zhigang;Zhang, Tiejun;Gan, Qi;Yang, Yuan;Chen, Tengyun;Huang, Bowen;Yang, Xiang;Xiao, Anqi;Ou, Yun;Su, Zhengzheng;Chen, Lu;Zhang, Yan;Ju, Yan;Zhang, Yuekang;Wang, Yuan
弥漫性中线胶质瘤-H3K27M突变型(DMG)和胶质母细胞瘤(GBM)分别是最致命的脑肿瘤，分别发生在儿童和成人患者。这两种肿瘤都表现出明显的异质性，受不同的遗传/表观遗传驱动因素、转录程序(包括RNA剪接)和胶质瘤微环境因素的影响。然而，细胞状态的空间组织和特定于生态位的调节程序仍有待调查。在这里，我们对DMG和GBM进行了空间分析，结合了短读和长读空间转录，以及单细胞转录数据集。我们确定了临床上相关的转录程序，RNA异构体多样性，以及不同胶质瘤生态位中的多细胞生态系统。我们发现，虽然肿瘤核心富含少突胶质前体样细胞，但放射状胶质干样细胞(RG样细胞)在DMG和GBM富含神经元的侵袭性壁龛中富含。此外，我们确定了针对RG样细胞的小生境特异性调节程序，并在功能上证实了FAM20C在人类神经干细胞衍生的原位DMG模型中介导了RG样细胞在富含神经元的微环境中的侵袭性生长。总而言之，我们的结果为理解DMG和GBM的空间架构和特定的利基漏洞提供了蓝图。弥漫性中线胶质瘤-H3K27M突变体(DMG)和胶质母细胞瘤(GBM)的空间组织仍有待研究。在这里，作者整合了DMG和GBM的短读和长读空间图谱，以确定不同胶质瘤利基环境中的调节程序和细胞生态系统。
Diffuse midline glioma-H3K27M mutant (DMG) and glioblastoma (GBM) are the most lethal brain tumors that primarily occur in pediatric and adult patients, respectively. Both tumors exhibit significant heterogeneity, shaped by distinct genetic/epigenetic drivers, transcriptional programs including RNA splicing, and microenvironmental cues in glioma niches. However, the spatial organization of cellular states and niche-specific regulatory programs remain to be investigated. Here, we perform a spatial profiling of DMG and GBM combining short- and long-read spatial transcriptomics, and single-cell transcriptomic datasets. We identify clinically relevant transcriptional programs, RNA isoform diversity, and multi-cellular ecosystems across different glioma niches. We find that while the tumor core enriches for oligodendrocyte precursor-like cells, radial glial stem-like (RG-like) cells are enriched in the neuron-rich invasive niche in both DMG and GBM. Further, we identify niche-specific regulatory programs for RG-like cells, and functionally confirm that FAM20C mediates invasive growth of RG-like cells in a neuron-rich microenvironment in a human neural stem cell derived orthotopic DMG model. Together, our results provide a blueprint for understanding the spatial architecture and niche-specific vulnerabilities of DMG and GBM. The spatial organisation of diffuse midline glioma-H3K27M mutant (DMG) and glioblastoma (GBM) remains to be investigated. Here, the authors integrate short-read and long-read spatial profiling of DMG and GBM to identify regulatory programs and cellular ecosystems in distinct glioma niches.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
一个 iCRISPR 平台，用于在人类多能干细胞中进行快速、可多重、可诱导的基因组编辑。
影响因子：
23.9
作者：
Gonzalez, Federico;Zhu, Zengrong;Shi, Zhong-Dong;Lelli, Katherine;Verma, Nipun;Li, Qing V.;Huangfu, Danwei
通讯作者：
Huangfu, Danwei
影响因子：
5.7
作者：
Faibish M;Francescone R;Bentley B;Yan W;Shao R
通讯作者：
Shao R
DOI：
10.1038/s41568-021-00397-3
发表时间：
2021-12
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Andersen BM;Faust Akl C;Wheeler MA;Chiocca EA;Reardon DA;Quintana FJ
通讯作者：
Quintana FJ
影响因子：
15.9
作者：
Krieger TG;Tirier SM;Park J;Jechow K;Eisemann T;Peterziel H;Angel P;Eils R;Conrad C
通讯作者：
Conrad C