{"title":"利用空间和单细胞转录组学全面绘制体细胞垂体神经内分泌肿瘤异质性图谱","authors":"Jialin Wang, Xuejing Li, Jing Guo, Zan Yuan, Xinyu Tong, Zehao Xiao, Meng Liu, Changxiaofeng Liu, Hongyun Wang, Lei Gong, Chuzhong Li, Yazhuo Zhang, Weiyan Xie, Chunhui Liu","doi":"10.1002/ctm2.70090","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Pituitary neuroendocrine tumours (PitNETs) are common intracranial tumours that are highly heterogeneous with unpredictable growth patterns. The driver genes and mechanisms that are crucial for tumour progression in somatotroph PitNETs are poorly understood.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>In this study, we performed integrative spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq) analysis on somatotroph tumours and normal pituitary samples to comprehensively characterize the differences in cellular characteristics.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>By analyzing combined copy number variations (CNVs), tumour tissues were divided into two regions, which included the CNV<sub>high</sub> and CNV<sub>low</sub> areas. The protumour genes DLK1 and RCN1 were highly expressed in the CNV<sub>high</sub> area, which might be related to tumour progression and could be targeted for precision therapy. We also found that the transforming growth factor beta signalling pathway participated in tumour progression and identified heterogeneity in the expression profiles of key genes. We assessed the intertumoral and intratumoral heterogeneity in somatotroph PitNETs and emphasized the importance of individualized treatment.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>In summary, we visualized the cellular distribution and transcriptional differences in normal pituitary and somatotroph PitNETs by ST and scRNA-seq for the first time. This study provides a strong theoretical foundation to comprehensively understand the crucial mechanisms involved in tumour progression and develop new strategies to treat somatotroph PitNETs.</p>\n </section>\n \n <section>\n \n <h3> Key points</h3>\n \n <div>\n <ul>\n \n <li>The first-ever visualization of cellular distributions in normal and tumor pituitary tissues.</li>\n \n <li>The inter- and intra-tumoral transcriptomic heterogeneity of somatotroph PitNETs was comprehensively revealed.</li>\n \n <li>Identification of potential protumor factors and critical signaling pathways, opening new avenues for therapeutic intervention.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"14 11","pages":""},"PeriodicalIF":7.9000,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11567828/pdf/","citationCount":"0","resultStr":"{\"title\":\"Comprehensive mapping of somatotroph pituitary neuroendocrine tumour heterogeneity using spatial and single-cell transcriptomics\",\"authors\":\"Jialin Wang, Xuejing Li, Jing Guo, Zan Yuan, Xinyu Tong, Zehao Xiao, Meng Liu, Changxiaofeng Liu, Hongyun Wang, Lei Gong, Chuzhong Li, Yazhuo Zhang, Weiyan Xie, Chunhui Liu\",\"doi\":\"10.1002/ctm2.70090\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Pituitary neuroendocrine tumours (PitNETs) are common intracranial tumours that are highly heterogeneous with unpredictable growth patterns. The driver genes and mechanisms that are crucial for tumour progression in somatotroph PitNETs are poorly understood.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>In this study, we performed integrative spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq) analysis on somatotroph tumours and normal pituitary samples to comprehensively characterize the differences in cellular characteristics.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>By analyzing combined copy number variations (CNVs), tumour tissues were divided into two regions, which included the CNV<sub>high</sub> and CNV<sub>low</sub> areas. The protumour genes DLK1 and RCN1 were highly expressed in the CNV<sub>high</sub> area, which might be related to tumour progression and could be targeted for precision therapy. We also found that the transforming growth factor beta signalling pathway participated in tumour progression and identified heterogeneity in the expression profiles of key genes. We assessed the intertumoral and intratumoral heterogeneity in somatotroph PitNETs and emphasized the importance of individualized treatment.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>In summary, we visualized the cellular distribution and transcriptional differences in normal pituitary and somatotroph PitNETs by ST and scRNA-seq for the first time. 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引用次数: 0
摘要
背景：垂体神经内分泌肿瘤（PitNETs）是一种常见的颅内肿瘤，具有高度异质性和不可预测的生长模式。人们对嗜体细胞性垂体神经内分泌肿瘤（PitNETs）肿瘤进展的驱动基因和机制知之甚少：在这项研究中，我们对嗜体细胞肿瘤和正常垂体样本进行了空间转录组学（ST）和单细胞RNA测序（scRNA-seq）综合分析，以全面描述细胞特征的差异：通过分析合并拷贝数变异（CNV），肿瘤组织被分为两个区域，包括CNV高区和CNV低区。原肿瘤基因DLK1和RCN1在CNV高区高表达，这可能与肿瘤进展有关，可作为精准治疗的靶点。我们还发现转化生长因子β信号通路参与了肿瘤的进展，并确定了关键基因表达谱的异质性。我们评估了瘤间和瘤内的异质性，强调了个体化治疗的重要性：总之，我们通过 ST 和 scRNA-seq 技术首次直观地了解了正常垂体和嗜体细胞 PitNET 的细胞分布和转录差异。这项研究为全面了解肿瘤进展的关键机制和开发治疗体细胞嗜养型PitNETs的新策略提供了坚实的理论基础：首次观察到正常和肿瘤垂体组织中的细胞分布。全面揭示了瘤间和瘤内的转录组异质性。确定了潜在的原发肿瘤因子和关键信号通路，为治疗干预开辟了新途径。
Comprehensive mapping of somatotroph pituitary neuroendocrine tumour heterogeneity using spatial and single-cell transcriptomics
Background
Pituitary neuroendocrine tumours (PitNETs) are common intracranial tumours that are highly heterogeneous with unpredictable growth patterns. The driver genes and mechanisms that are crucial for tumour progression in somatotroph PitNETs are poorly understood.
Methods
In this study, we performed integrative spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq) analysis on somatotroph tumours and normal pituitary samples to comprehensively characterize the differences in cellular characteristics.
Results
By analyzing combined copy number variations (CNVs), tumour tissues were divided into two regions, which included the CNVhigh and CNVlow areas. The protumour genes DLK1 and RCN1 were highly expressed in the CNVhigh area, which might be related to tumour progression and could be targeted for precision therapy. We also found that the transforming growth factor beta signalling pathway participated in tumour progression and identified heterogeneity in the expression profiles of key genes. We assessed the intertumoral and intratumoral heterogeneity in somatotroph PitNETs and emphasized the importance of individualized treatment.
Conclusion
In summary, we visualized the cellular distribution and transcriptional differences in normal pituitary and somatotroph PitNETs by ST and scRNA-seq for the first time. This study provides a strong theoretical foundation to comprehensively understand the crucial mechanisms involved in tumour progression and develop new strategies to treat somatotroph PitNETs.
Key points
The first-ever visualization of cellular distributions in normal and tumor pituitary tissues.
The inter- and intra-tumoral transcriptomic heterogeneity of somatotroph PitNETs was comprehensively revealed.
Identification of potential protumor factors and critical signaling pathways, opening new avenues for therapeutic intervention.
期刊介绍：
Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.
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