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<p>Although adamantinomatous craniopharyngioma (ACP) is a histologically benign intracranial tumor, its invasive growth pattern, characterized by finger-like protrusions, leads to a poor prognosis. In-depth analysis of the heterogeneity of the pathological structure of ACP and the development and evolution of tumor cells is crucial for expanding precision treatment strategies. However, a detailed understanding of the complex pathological structural characteristics of ACP is lacking. Here, we used laser microdissection to obtain 40 samples from 6 different pathological structures for Smart-Seq2 sequencing and conducted in-depth analysis of 6 single-nucleus RNA sequencing samples and 4 spatial transcriptome samples. We also performed comprehensive validation using 3 external single-cell databases. Through histopathological observation, multiomic analysis, and immunofluorescence staining, we resolved the single-cell expression profiles of two distinct functional subpopulations of the whorl-like cell clusters, providing insights into their potential biological roles in tumor progression. Additionally, we discovered the epithelial–mesenchymal transition (EMT) or partial EMT development direction of the stellate reticulum and different cell fates related to terminal keratinization. Moreover, we reported the presence of previously neglected cyst-wall epithelium and the constitutive epithelium within ACP. The latter was found to possess basal cell characteristics and act as a potential progenitor cell pool for tumor maintenance and evolution. Through pseudotime analysis combined with co-expression network analysis, we constructed a differentiation regulatory network based on the constitutive epithelium. Our research results complement existing knowledge and provide a comprehensive analysis of the pathological features of ACP, providing new concepts and targets for precision targeted therapy. </p>

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Laser microdissection-based multi-omics integration unveils the pathological atlas and tumor differentiation network of adamantinomatous craniopharyngioma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月9日

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  • Bowen Wu,
  • Chunming Xu,
  • Chenxing Yang,
  • Shenhao Xie,
  • Suping Duan,
  • Jiye Ye,
  • Jinshi Zhang,
  • Shaoyang Li,
  • Furong Liang,
  • Zhicheng Ye,
  • Hai Luo,
  • Rilege Su,
  • Laisheng Pan,
  • Zhizheng Liu,
  • Shizhou Xing,
  • Tianming Dong,
  • Yiguang Chen,
  • Like Chen,
  • Suyue Zheng,
  • Jie Wu,
  • Tao Hong

摘要

Although adamantinomatous craniopharyngioma (ACP) is a histologically benign intracranial tumor, its invasive growth pattern, characterized by finger-like protrusions, leads to a poor prognosis. In-depth analysis of the heterogeneity of the pathological structure of ACP and the development and evolution of tumor cells is crucial for expanding precision treatment strategies. However, a detailed understanding of the complex pathological structural characteristics of ACP is lacking. Here, we used laser microdissection to obtain 40 samples from 6 different pathological structures for Smart-Seq2 sequencing and conducted in-depth analysis of 6 single-nucleus RNA sequencing samples and 4 spatial transcriptome samples. We also performed comprehensive validation using 3 external single-cell databases. Through histopathological observation, multiomic analysis, and immunofluorescence staining, we resolved the single-cell expression profiles of two distinct functional subpopulations of the whorl-like cell clusters, providing insights into their potential biological roles in tumor progression. Additionally, we discovered the epithelial–mesenchymal transition (EMT) or partial EMT development direction of the stellate reticulum and different cell fates related to terminal keratinization. Moreover, we reported the presence of previously neglected cyst-wall epithelium and the constitutive epithelium within ACP. The latter was found to possess basal cell characteristics and act as a potential progenitor cell pool for tumor maintenance and evolution. Through pseudotime analysis combined with co-expression network analysis, we constructed a differentiation regulatory network based on the constitutive epithelium. Our research results complement existing knowledge and provide a comprehensive analysis of the pathological features of ACP, providing new concepts and targets for precision targeted therapy.