Single cell RNA sequencing of multiple myeloma I. Single cell RNA sequencing of multiple myeloma I

To understand molecular events associated with myeloma progression, we applied single-cell RNA sequencing to myeloma cells in the bone marrow and extramedullary sites. Transcriptome analysis, at single cell level, demonstrates that proliferation and alterations in antigen presentation are associated with myeloma progression whereas NF-kB pathway activation has an anti-correlation. While these alterations are prominent in most of the extramedullary myeloma cells, some myeloma cells in the bone marrow show gene expression signatures resembling extramedullary cells even when the myeloma cells were taken at stable disease. Altogether single-cell transcriptome analysis reveals both common transcriptional programs and heterogeneity turned on during myeloma progression. Overall design: We performed single cell RNA sequencing (RNA-seq) for multiple myeloma from the bone marrow and/or extramedullary sites from 10 patients. Additional bulk RNA sequencing was performed with CD138-negative non-myeloma populations from the same patients. Data contain 477 single-cell RNA-seq and 11 bulk RNA-seq.

为解析与多发性骨髓瘤进展相关的分子事件，本研究对骨髓及髓外部位的骨髓瘤细胞开展了单细胞RNA测序（single-cell RNA sequencing）。单细胞层面的转录组分析结果显示，细胞增殖与抗原呈递异常与骨髓瘤进展呈正相关，而核因子κB（NF-κB）通路激活则与之呈负相关。尽管这类异常在多数髓外骨髓瘤细胞中较为显著，但部分骨髓内骨髓瘤细胞即便在疾病稳定阶段取材，其基因表达特征也与髓外骨髓瘤细胞高度相似。综上，单细胞转录组分析揭示了骨髓瘤进展过程中激活的共有转录程序与细胞异质性。整体实验设计：本研究对10例患者的骨髓及/或髓外部位的多发性骨髓瘤细胞进行了单细胞RNA测序。同时，对同一患者体内CD138阴性的非骨髓瘤细胞群体开展了批量RNA测序。本数据集共包含477条单细胞RNA测序数据与11条批量RNA测序数据。