Single-cell RNA sequencing analysis revealed a potential association between ELK3 expression and the progression of multiple myeloma.

Background: Multiple myeloma (MM) typically evolves from monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Its progression is accompanied by significant tumor heterogeneity and immune microenvironment remodeling, and MM remains largely incurable despite therapeutic advances. Elucidating cellular heterogeneity and regulatory mechanisms involved in disease progression is critical for understanding MM pathogenesis. Methods: Single-cell RNA sequencing (scRNA-seq) provides important support for systematically elucidating the molecular mechanisms and immune regulatory pathways associated with the progression of MM. The scRNA-seq datasets from healthy donors (HD), MGUS, SMM, and MM patients were obtained from the GEO database to analyze plasma cell transcriptional heterogeneity within the bone marrow microenvironment. Plasma cell differentiation trajectories were inferred using pseudotime analysis, and intercellular communication and transcription factor regulatory networks were predicted using CellChat and SCENIC analyses. In addition, functional validation of Results: In this work, we used scRNA-seq to thoroughly evaluate the heterogeneity of MM. We identified a tumor-associated plasma cell subtype, C4 Conclusion: In summary, this study, based on scRNA-seq analysis, identified a C4