Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
Institute of Clinical Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China.
Sci Adv. 2023 Apr 14;9(15):eadc8933. doi: 10.1126/sciadv.adc8933. Epub 2023 Apr 12.
Despite improvements in microscopically neurosurgical techniques made in recent years, the prognosis of adamantinomatous craniopharyngioma (ACP) is still unsatisfactory. Little is known about cellular atlas and biological features of ACP. Here, we carried out integrative analysis of 44,038 single-cell transcriptome profiles to characterize the landscape of intratumoral heterogeneity and tumor microenvironment (TME) in ACP. Four major neoplastic cell states with distinctive expression signatures were defined, which further revealed the histopathological features and elucidated unknown cellular atlas of ACP. Pseudotime analyses suggested potential evolutionary trajectories between specific neoplastic cell states. Notably, a distinct oligodendrocyte lineage was identified in ACP, which was associated with immunological infiltration and neural damage. In addition, we described a tumor-centric regulatory network based on intercellular communication in TME. Together, our findings represent a unique resource for deciphering tumor heterogeneity of ACP, which will improve clinical diagnosis and treatment strategies.
尽管近年来在显微镜神经外科技术方面取得了进步,但造釉细胞瘤型颅咽管瘤(adamantinomatous craniopharyngioma,ACP)的预后仍然不尽人意。人们对 ACP 的细胞图谱和生物学特征知之甚少。在这里,我们对 44038 个单细胞转录组谱进行了综合分析,以描绘 ACP 肿瘤内异质性和肿瘤微环境(tumor microenvironment,TME)的全景。确定了具有独特表达特征的四个主要肿瘤细胞状态,进一步揭示了 ACP 的组织病理学特征和未知的细胞图谱。拟时分析表明特定肿瘤细胞状态之间存在潜在的进化轨迹。值得注意的是,在 ACP 中鉴定出了一个独特的少突胶质细胞谱系,它与免疫浸润和神经损伤有关。此外,我们还描述了基于 TME 细胞间通讯的以肿瘤为中心的调控网络。总之,我们的研究结果代表了破译 ACP 肿瘤异质性的独特资源,这将改善临床诊断和治疗策略。