Single cell sequencing for diffuse large B cells. Homo sapiens

Diffuse large B-cell lymphoma (DLBCL) is the predominant type in central nervous system lymphoma (CNSL) including primary CNSL and secondary CNSL. Diffuse large B cells in cerebrospinal fluid (CSF-DLBCs) have offered great promise for the diagnostics and therapeutics of CNSL leptomeningeal involvement. To explore the distinct phenotypic states of CSF-DLBCs, we analyzed the transcriptomes of 902 CSF-DLBCs from six CNSL-DLBCL patients using single-cell RNA sequencing technology. We defined CSF-DLBCs based on abundant expression of B-cell markers, as well as the enrichment of cell proliferation and energy metabolism pathway. CSF-DLBCs within individual patient have monoclonality with similar variable region of light chains (VL) expression. It is interesting to find some CSF-DLBCs have double classes of VL (lambda and kappa) transcripts. We identified substantial heterogeneity in CSF-DLBCs, and found significantly greater among-patient heterogeneity compared to among-cell heterogeneity within patient. The transcriptional heterogeneity across CSF-DLBCs are manifested in cell cycle state and cancer-testis antigens expression. Our results will provide insight into the mechanism research and new diagnostic direction of CNSL-DLBCL leptomeningeal involvement.