Single-cell transcriptome analysis of diffuse large B cells in cerebrospinal fluid of central nervous system lymphoma

中枢神经系统淋巴瘤脑脊液弥漫大B细胞的单细胞转录组分析

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作者:Haoyu Ruan, Zhe Wang, Yue Zhai, Ying Xu, Linyu Pi, Jihong Zheng, Yihang Zhou, Cong Zhang, Ruofan Huang, Kun Chen, Xiangyu Li, Weizhe Ma, Zhiyuan Wu, Jie Shen, Xuan Deng, Chao Zhang, Ming Guan

Abstract

Diffuse large B cells in the cerebrospinal fluid (CSF-DLBCs) have offered great promise for the diagnostics and therapeutics of central nervous system lymphoma (CNSL) leptomeningeal involvement. To explore the phenotypic states of CSF-DLBCs, we analyzed the transcriptomes of more than one thousand CSF-DLBCs from six patients with CNSL diffuse large B-cell lymphoma (DLBCL) using Smart-seq2 single-cell RNA sequencing. CSF-DLBCs were defined based on abundant expression of B-cell markers, the active cell proliferation and energy metabolism properties, and immunoglobulin light chain restriction. We identified inherent heterogeneity of CSF-DLBCs, which were mainly manifested in cell cycle state, cancer-testis antigen expression, and classification based on single-cell germinal center B-cell signature. In addition, the 16 upregulated genes in CSF-DLBCs compared to various normal B cells showed great possibility in the homing effect of the CNS-DLBCL for the leptomeninges. Our results will provide insight into the mechanism research and diagnostic direction of CNSL-DLBCL leptomeningeal involvement.

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