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通过单细胞 RNA 测序研究高表达 TP53 的骨肉瘤细胞在肿瘤微环境中的细胞通讯和信号通路。

Investigation of cellular communication and signaling pathways in tumor microenvironment for high TP53-expressing osteosarcoma cells through single-cell RNA sequencing.

机构信息

Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China.

Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning, 530021, China.

出版信息

Med Oncol. 2024 Mar 25;41(5):93. doi: 10.1007/s12032-024-02318-4.

Abstract

Osteosarcoma (OS) stands as the most prevalent primary bone cancer in children and adolescents, and its limited treatment options often result in unsatisfactory outcomes, particularly for metastatic cases. The tumor microenvironment (TME) has been recognized as a crucial determinant in OS progression. However, the intercellular dynamics between high TP53-expressing OS cells and neighboring cell types within the TME are yet to be thoroughly understood. In our study, we harnessed the single-cell RNA sequencing (scRNA-seq) technology in combination with the computational tool-Cellchat, aiming to elucidate the intercellular communication networks present within OS. Through meticulous quantitative inference and subsequent analysis of these networks, we succeeded in identifying significant signaling pathways connecting high TP53-expressing OS cells with proximate cell types, namely Macrophages, Monocytes, Endothelial Cells, and PVLs. This research brings forth a nuanced understanding of the intricate patterns and coordination involved in the TME's intercellular communication signals. These findings not only provide profound insights into the molecular mechanisms underpinning OS but also indicate potential therapeutic targets that could revolutionize treatment strategies.

摘要

骨肉瘤(OS)是儿童和青少年中最常见的原发性骨癌,其治疗选择有限,往往导致结果不理想,特别是转移性病例。肿瘤微环境(TME)已被认为是 OS 进展的关键决定因素。然而,高表达 TP53 的 OS 细胞与 TME 中邻近细胞类型之间的细胞间动力学仍未被充分理解。在我们的研究中,我们利用单细胞 RNA 测序(scRNA-seq)技术结合计算工具-Cellchat,旨在阐明 OS 内存在的细胞间通讯网络。通过对这些网络进行细致的定量推断和后续分析,我们成功地鉴定出了将高表达 TP53 的 OS 细胞与邻近细胞类型(即巨噬细胞、单核细胞、内皮细胞和 PVLs)连接起来的重要信号通路。这项研究深入了解了 TME 细胞间通讯信号中涉及的复杂模式和协调。这些发现不仅为 OS 的分子机制提供了深刻的见解,还指出了可能改变治疗策略的潜在治疗靶点。

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