Scholarlink

Background <p>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.</p> Methods <p>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.</p> Results <p>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”.</p> Conclusions <p>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 evasion. A prognostic model based on HMGhMSC subpopulations was developed, which demonstrated that these cells have significant potential as therapeutic targets for improving the prognosis and developing treatments for bone disease in multiple myeloma patients.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月16日

查看全文
  • Fei-Er Ju,
  • Bei-Hui Huang,
  • Hao Wu,
  • Bo Zou,
  • Shu-Na Chen,
  • Xiao-Yan Sang,
  • Wei-Yao Liang,
  • Zi-Xuan Liu,
  • Zi-Xuan Zhang,
  • Zi-Yi Yang,
  • Yan-Ting Liang,
  • Yue-Lan Liang,
  • Huan Liu,
  • Zhao-Xia Dong,
  • Xue-Qi Liu,
  • Li-Yuan Zheng,
  • Jin-Cheng Zeng,
  • Jin-Heng Wang,
  • Lin Qi,
  • Xing-Ding Zhang,
  • Yongjiang Zheng,
  • Juan Li

摘要

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 evasion. A prognostic model based on HMGhMSC subpopulations was developed, which demonstrated that these cells have significant potential as therapeutic targets for improving the prognosis and developing treatments for bone disease in multiple myeloma patients.