Integrative analysis of bulk and single-cell gene expression profiles to identify bone marrow mesenchymal cell heterogeneity and prognostic significance in multiple myeloma

作者：Fei‐er Ju, Bei-Hui Huang, Hao Wu, Bo Zou, Shu‐Na Chen, Xiaoyan Sang, Wei Liang, Zi‐xuan Liu, Zixuan Zhang, Ziyi Yang, Yan-Ting Liang, Yuelan Liang, Huan Liu, Zhao-Xia Dong, Xue‐Qi Liu, Liyuan Zheng, Jincheng Zeng, Jin-Heng Wang, Lin Qi, Xing‐Ding Zhang, Yongjiang Zheng, Juan Li · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-06637-6 · 被引用次数：2 · 研究领域：Multiple Myeloma Research and Treatments、Single-cell and spatial transcriptomics、Mesenchymal stem cell research

BACKGROUND: Multiple myeloma is a hematologic malignancy characterized by complex interactions within the tumor microenvironment, where mesenchymal stem cells (MSCs) contribute significantly to disease progression, immune suppression, and drug resistance. METHODS: This study investigated the heterogeneity of MSCs in multiple myeloma using single-cell RNA sequencing (10X) and bulk transcriptomic data. Further analysis was performed by Seurat, SCENIC, CellChat. GSE4581 and GSE136337 were used as training set and validation set to construct a newly described prognostic model through COX and LASSO. RESULTS: By analyzing bone marrow samples from healthy donors and multiple myeloma patients at different Revised International Staging System (R-ISS) stages, this study identified distinct MSC subpopulations, including osteogenic, angiogenic, immune regulatory, and multipotent clusters, each of which plays unique roles in the tumor microenvironment. Interestingly, we found a unique subclone with upregulated expression of high mobility group proteins, these MSC exert a strong regulatory effect, which was defined as "HMGhMSC". CONCLUSIONS: Our findings reveal that the proportion of osteogenic MSCs, which are crucial for bone health, decreases as the disease progresses, which is correlated with the bone lysis commonly observed in advanced multiple myeloma. Additionally, immune regulatory MSCs contribute to the formation of an immunosuppressive microenvironment, promoting tumor immune evas...