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中弥漫性大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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