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Surveying brain tumor heterogeneity by single-cell RNA-sequencing of multi-sector biopsies

查看全文 作  者:Kai [1]Yu;Yuqiong [1,2,3]Hu;Fan [4,5,6]Wu;Qiufang [1]Guo;Zenghui [5]Qian;Waner [1]Hu;Jing [4,5,6]Chen;Kuanyu [4,5,6]Wang;Xiaoying [1,2,3]Fan;Xinglong [2,3,7]Wu;John EJ [8,9]Rasko;Xiaolong [10]Fan;Antonio [11,12,13]lavarone;Tao [4,5,6,14]Jiang;Fuchou [1,2,3,7]Tang;Xiao-Dong [1]Su 高影响力作者 机构地区:[1]Biomedical Pioneeung Innovation Center(BIOPIC),School of Life Sciences,Peking University.Beijing 100871,China;[2]Beijing Advanced Innovation Center for Genomics,School of Life Sciences,Peking University,Beijing 100871,China;[3]Biomedical Institute for Pioneering Investigation via Convergence and Center for Reproductive Medicine.Ministry of Education Key Laboratory of Cell Proliferation and Differentiation,Beijing 100871,China;[4]Department of Molecular Neuropathology,Beijing Neurosurgical Institute,Capital Medical University,Beijing 100050,China;[5]Department of Neurosurgery,Beijing Tiantan Hospital,Capital Medical University,Beijing 100050,China;[6]Chinese Glioma Genome Atlas Network(CGGA)and Asian Glioma Genome Atlas Network(AGGA),Beijing 100050,China;[7]Peking-Tsinghua Center for Life Sciences,Peking University,Beijing 100871,China;[8]Gene and Stem Cell Therapy Program,Centenary Institute,University of Sydney,Sydney,NSW,Australia;[9]Department of Cell and Moleculai Therapies,Royal Prince Alfred Hospital,Sydney,NSW,Australia;[10]Beijing Key Laboratory of Gene Resource and Molecular Development,Laboratory of Neuroscience and Brain Development,Beijing Normal University,Beijing 100875.China;[11]Institute for Cancer Genetics,Herbert living Comprehensive Cancer Center,Columbia Univeisity Medical Center,New York,NY 10032,USA;[12]Department of Pathology&Cell Biology,Columbia University Medical Center,New York,NY 10032,USA;[13]Department of Neurology,Columbia University Medical Center,New York,NY 10032,USA;[14]Center of Brain Tumor,Beijing Institute for Brain Disorders,Beijing 100069,China高影响力机构 出  处:《National Science Review》索引2020年第7卷第8期,共13页高影响力期刊 摘  要:Brain tumors are among the most challenging human tumors for which the mechanisms driving progression and heterogeneity remain poorly understood.We combined single-cell RNA-seq with multi-sector biopsies to sample and analyze single-cell expression profiles of gliomas from 13 Chinese patients.After classifying individual cells;we generated a spatial and temporal landscape of glioma that revealed the patterns of invasion between the different sub-regions of gliomas.We also used single-cell inferred copy number variations and pseudotime trajectories to inform on the crucial branches that dominate tumor progression.The dynamic cell components of the multi-region biopsy analysis allowed us to spatially deconvolute with unprecedented accuracy the transcriptomic features of the core and those of the periphery of glioma at single-cell level.Through this rich and geographically detailed dataset,we were also able to characterize and construct the chemokine and chemokine receptor interactions that exist among different tumor and non-tumor cells.This study provides the first spatial-level analysis of the cellular states that characterize human gliomas.It also presents an initial molecular map of the cross-talks between glioma cells and the surrounding microenvironment with single-cell resolution. 关 键 词:glioma HETEROGENEITY multi-sector biopsy single-cell RNA-seq
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