GSE176131
Identification of heterogeneous networks and plasma-monocytes crosstalks in multiple myeloma stratified by R-ISS system through single-cell sequencing
Purpose: to identify new potential pathways and therapeutic targets to kill plasma cells and affect their microenvironment in stage R-ISS III MM patients. Methods: We performed single-cell RNA sequencing of bone marrow samples obtained from nine MM patients and from two normal controls including pseudotime analysis, SCENIC analysis,cell–cell communication networks,large-scale chromosomal CNV analysis.The new markers that we reported originally were verified by qPCR, flow cytometry and immunofluorescence staining. Results: We identified two R-ISS-related modules, namely, “protein metabolism” (module 2) and “cell proliferation” (module 1). The gene expression pattern in pseudotime suggested that the gene activation in module 2 provides a substantial basis for the malignant proliferation of plasma cells during MM progression. We found that STAT1 may activate LETM1 to promote MM progression via the C-type lectin receptor signaling pathway. And PDIA6 was putatively activated by the UQCRB regulon to participate in oxidative phosphorylation. Moreover, a subcluster of monocytes exclusively found in stage III and specifically expressed CCL3L1, CCL3, and CXCL2 was modulated by ATF3. CCL3/CCL5/CCL3L1–CCR1, CCL4–SLC7A1, CD47–SIPRA, SEMA4A–PLXND1, and LILRB4–LAIR1 were identified as the active ligand–receptor pairs in plasma–monocyte communications in stage III. Conclusions: we systematically analyzed the molecular events and the regulated networks in the progression of the R-ISS stages, and the results suggested a promising landscape for the treatment of MM. Overall design: We performed single-cell RNA sequencing of bone marrow samples obtained from nine MM patients and from two normal controls to investigate the heterogeneity among the stages stratified by R-ISS (Revised International Staging System)