RT Journal Article SR Electronic T1 Surveying Brain Tumor Heterogeneity by Single-Cell RNA Sequencing of Multi-sector Biopsies JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.01.19.911701 DO 10.1101/2020.01.19.911701 A1 Kai Yu A1 Yuqiong Hu A1 Fan Wu A1 Qiufang Guo A1 Zenghui Qian A1 Waner Hu A1 Jing Chen A1 Kuanyu Wang A1 Xiaoying Fan A1 Xinglong Wu A1 John EJ Rasko A1 Xiaolong Fan A1 Antonio Iavarone A1 Tao Jiang A1 Fuchou Tang A1 Xiao-Dong Su YR 2020 UL http://biorxiv.org/content/early/2020/04/04/2020.01.19.911701.abstract AB 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 multisector 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 CNVs 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 crosstalks between glioma cells and the surrounding microenvironment with single cell resolution.