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

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

doi:10.1016/j.isci.2021.102972

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

iScience. 2021 Aug 11;24(9):102972. doi: 10.1016/j.isci.2021.102972. eCollection 2021 Sep 24.

Authors

Haoyu Ruan^{1

2}, Zhe Wang³, Yue Zhai⁴, Ying Xu⁴, Linyu Pi⁴, Jihong Zheng⁴, Yihang Zhou⁴, Cong Zhang³, Ruofan Huang⁵, Kun Chen⁶, Xiangyu Li⁶, Weizhe Ma⁷, Zhiyuan Wu⁶, Jie Shen⁸, Xuan Deng¹, Chao Zhang³, Ming Guan¹

Affiliations

¹ Department of Clinical Laboratory, Huashan Hospital, Fudan University, Shanghai, China.
² Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
³ Department of Plastic and Reconstructive Surgery, Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
⁵ Department of Oncology, Huashan Hospital, Fudan University, Shanghai, China.
⁶ Department of Clinical Laboratory, Huashan Hospital North, Fudan University, Shanghai, China.
⁷ Central Laboratory, Huashan Hospital, Fudan University, Shanghai, China.
⁸ 10K Genomics Technology Co.,Ltd., 333 Guiping Road, Shanghai 200233, China.

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.

Keywords: Bioinformatics; Biological sciences; Immunology; Neuroscience; Omics.