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人类骨肉瘤的单细胞和空间分辨图谱。

A single-cell and spatially resolved atlas of human osteosarcomas.

机构信息

Departments of Orthopedics, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Department of Orthopedics, Peking University First Hospital, Beijing, 100021, China.

出版信息

J Hematol Oncol. 2024 Aug 20;17(1):71. doi: 10.1186/s13045-024-01598-7.

DOI:10.1186/s13045-024-01598-7
PMID:39164791
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11337771/
Abstract

Osteosarcomas are intricate cellular ecosystems, where heterotypic interactions significantly influence disease progression and therapeutic outcomes. Despite their importance, a detailed understanding of their cellular composition and organizational structure remains elusive. In this study, we provide a comprehensive single-cell and spatially resolved transcriptomics analysis of human osteosarcomas. We construct a cellular meta-map to dissect spatial transcriptomic data, unveiling a detailed atlas of osteosarcoma compositional subgroups. We meticulously characterize the unique gene signatures and functional states of each subgroup and investigate the impact of chemotherapy on these cellular subpopulations. Additionally, our spatial transcriptomics analysis identifies a distinct spatial niche, located at the forefront of tumor necrotic zones, potentially associated with chemotherapy resistance. We also delve into the crosstalk between different cellular subgroups. This study furnishes a comprehensive transcriptional atlas of osteosarcoma's cellular architecture, enriching our comprehension of its complexity and laying the groundwork for more targeted therapeutic approaches.

摘要

骨肉瘤是复杂的细胞生态系统,异型相互作用对疾病进展和治疗结果有重要影响。尽管它们很重要,但对其细胞组成和组织结构的详细了解仍难以捉摸。在这项研究中,我们对人类骨肉瘤进行了全面的单细胞和空间分辨转录组学分析。我们构建了一个细胞元图来剖析空间转录组数据,揭示了骨肉瘤组成亚群的详细图谱。我们仔细描述了每个亚群的独特基因特征和功能状态,并研究了化疗对这些细胞亚群的影响。此外,我们的空间转录组学分析还确定了一个位于肿瘤坏死区前沿的独特空间生态位,该生态位可能与化疗耐药性有关。我们还深入探讨了不同细胞亚群之间的串扰。这项研究提供了骨肉瘤细胞结构的全面转录组图谱,丰富了我们对其复杂性的理解,并为更有针对性的治疗方法奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0dc/11337771/b18a441dc0a6/13045_2024_1598_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0dc/11337771/d2608b444af2/13045_2024_1598_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0dc/11337771/b18a441dc0a6/13045_2024_1598_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0dc/11337771/d2608b444af2/13045_2024_1598_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0dc/11337771/b18a441dc0a6/13045_2024_1598_Fig2_HTML.jpg

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本文引用的文献

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Front Oncol. 2021 Jul 21;11:709210. doi: 10.3389/fonc.2021.709210. eCollection 2021.
2
A first-generation pediatric cancer dependency map.第一代儿科癌症依赖图谱。
Nat Genet. 2021 Apr;53(4):529-538. doi: 10.1038/s41588-021-00819-w. Epub 2021 Mar 22.
3
Single-cell RNA landscape of intratumoral heterogeneity and immunosuppressive microenvironment in advanced osteosarcoma.
Immunosuppressive Tumor Microenvironment of Osteosarcoma.
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Cancers (Basel). 2025 Jun 24;17(13):2117. doi: 10.3390/cancers17132117.
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Harnessing multi‑omics to revolutionize understanding and management of osteosarcoma: A pathway to precision medicine (Review).利用多组学技术革新骨肉瘤的认识与管理:精准医学之路(综述)
Int J Mol Med. 2025 Jun;55(6). doi: 10.3892/ijmm.2025.5533. Epub 2025 Apr 17.
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Single-Cell Spatial-Temporal Analysis of in Mediating Drug Resistance and CD8 T Cell Dysfunction.介导耐药性和CD8 T细胞功能障碍过程中的单细胞时空分析
Research (Wash D C). 2024 Nov 12;7:0530. doi: 10.34133/research.0530. eCollection 2024.
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