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.

中文翻译：

---

人类骨肉瘤的单细胞和空间分辨图谱


骨肉瘤是错综复杂的细胞生态系统，其中异型相互作用会显着影响疾病进展和治疗结果。尽管它们很重要，但对其细胞组成和组织结构的详细理解仍然难以捉摸。在这项研究中，我们提供了人骨肉瘤的全面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组的详细图谱。我们仔细表征了每个亚组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确定了一个独特的空间生态位，位于肿瘤坏死区的最前沿，可能与化疗耐药性有关。我们还深入研究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综合转录图谱，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。