Single-cell transcriptomic analysis reveals tumor cell heterogeneity and immune microenvironment features of pituitary neuroendocrine tumors
Abstract Background Pituitary neuroendocrine tumors (PitNETs) are one of the most common types of intracranial tumors. Currently, the cellular characteristics of normal pituitary and various other types of PitNETs are still not completely understood. Methods We performed single-cell RNA sequencing (...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Genome Medicine |
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| Online Access: | https://doi.org/10.1186/s13073-023-01267-3 |
| _version_ | 1827388246049423360 |
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| author | Nan Yan Weiyan Xie Dongfang Wang Qiuyue Fang Jing Guo Yiyuan Chen Xinqi Li Lei Gong Jialin Wang Wenbo Guo Xuegong Zhang Yazhuo Zhang Jin Gu Chuzhong Li |
| author_facet | Nan Yan Weiyan Xie Dongfang Wang Qiuyue Fang Jing Guo Yiyuan Chen Xinqi Li Lei Gong Jialin Wang Wenbo Guo Xuegong Zhang Yazhuo Zhang Jin Gu Chuzhong Li |
| author_sort | Nan Yan |
| collection | DOAJ |
| description | Abstract Background Pituitary neuroendocrine tumors (PitNETs) are one of the most common types of intracranial tumors. Currently, the cellular characteristics of normal pituitary and various other types of PitNETs are still not completely understood. Methods We performed single-cell RNA sequencing (scRNA-seq) on 4 normal samples and 24 PitNET samples for comprehensive bioinformatics analysis. Findings regarding the function of PBK in the aggressive tumor cells were validated by siRNA knockdown, overexpression, and transwell experiments. Results We first constructed a reference cell atlas of the human pituitary. Subsequent scRNA-seq analysis of PitNET samples, representing major tumor subtypes, shed light on the intrinsic cellular heterogeneities of the tumor cells and tumor microenvironment (TME). We found that the expression of hormone-encoding genes defined the major variations of the PIT1-lineage tumor cell transcriptomic heterogeneities. A sub-population of TPIT-lineage tumor cells highly expressing GZMK suggested a novel subtype of corticotroph tumors. In immune cells, we found two clusters of tumor-associated macrophages, which were both highly enriched in PitNETs but with distinct functional characteristics. In PitNETs, the stress response pathway was significantly activated in T cells. While a majority of these tumors are benign, our study unveils a common existence of aggressive tumor cells in the studied samples, which highly express a set of malignant signature genes. The following functional experiments confirmed the oncogenic role of selected up-regulated genes. The over-expression of PBK could promote both tumor cell proliferation and migration, and it was also significantly associated with poor prognosis in PitNET patients. Conclusions Our data and analysis manifested the basic cell types in the normal pituitary and inherent heterogeneity of PitNETs, identified several features of the tumor immune microenvironments, and found a novel epithelial cell sub-population with aggressive signatures across all the studied cases. |
| first_indexed | 2024-03-08T16:14:55Z |
| format | Article |
| id | doaj.art-08d8a2834ced46b39b32bc659bed0812 |
| institution | Directory Open Access Journal |
| issn | 1756-994X |
| language | English |
| last_indexed | 2024-03-08T16:14:55Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Medicine |
| spelling | doaj.art-08d8a2834ced46b39b32bc659bed08122024-01-07T12:37:55ZengBMCGenome Medicine1756-994X2024-01-0116111710.1186/s13073-023-01267-3Single-cell transcriptomic analysis reveals tumor cell heterogeneity and immune microenvironment features of pituitary neuroendocrine tumorsNan Yan0Weiyan Xie1Dongfang Wang2Qiuyue Fang3Jing Guo4Yiyuan Chen5Xinqi Li6Lei Gong7Jialin Wang8Wenbo Guo9Xuegong Zhang10Yazhuo Zhang11Jin Gu12Chuzhong Li13MOE Key Laboratory of Bioinformatics, Department of Automation, BNRIST Bioinformatics Division, Tsinghua UniversityBeijing Neurosurgical Institute, Capital Medical UniversityBiomedical Pioneering Innovative Center, Peking UniversityBeijing Neurosurgical Institute, Capital Medical UniversityBeijing Neurosurgical Institute, Capital Medical UniversityBeijing Neurosurgical Institute, Capital Medical UniversityMOE Key Laboratory of Bioinformatics, Department of Automation, BNRIST Bioinformatics Division, Tsinghua UniversityBeijing Neurosurgical Institute, Capital Medical UniversityBeijing Neurosurgical Institute, Capital Medical UniversityMOE Key Laboratory of Bioinformatics, Department of Automation, BNRIST Bioinformatics Division, Tsinghua UniversityMOE Key Laboratory of Bioinformatics, Department of Automation, BNRIST Bioinformatics Division, Tsinghua UniversityBeijing Neurosurgical Institute, Capital Medical UniversityMOE Key Laboratory of Bioinformatics, Department of Automation, BNRIST Bioinformatics Division, Tsinghua UniversityBeijing Neurosurgical Institute, Capital Medical UniversityAbstract Background Pituitary neuroendocrine tumors (PitNETs) are one of the most common types of intracranial tumors. Currently, the cellular characteristics of normal pituitary and various other types of PitNETs are still not completely understood. Methods We performed single-cell RNA sequencing (scRNA-seq) on 4 normal samples and 24 PitNET samples for comprehensive bioinformatics analysis. Findings regarding the function of PBK in the aggressive tumor cells were validated by siRNA knockdown, overexpression, and transwell experiments. Results We first constructed a reference cell atlas of the human pituitary. Subsequent scRNA-seq analysis of PitNET samples, representing major tumor subtypes, shed light on the intrinsic cellular heterogeneities of the tumor cells and tumor microenvironment (TME). We found that the expression of hormone-encoding genes defined the major variations of the PIT1-lineage tumor cell transcriptomic heterogeneities. A sub-population of TPIT-lineage tumor cells highly expressing GZMK suggested a novel subtype of corticotroph tumors. In immune cells, we found two clusters of tumor-associated macrophages, which were both highly enriched in PitNETs but with distinct functional characteristics. In PitNETs, the stress response pathway was significantly activated in T cells. While a majority of these tumors are benign, our study unveils a common existence of aggressive tumor cells in the studied samples, which highly express a set of malignant signature genes. The following functional experiments confirmed the oncogenic role of selected up-regulated genes. The over-expression of PBK could promote both tumor cell proliferation and migration, and it was also significantly associated with poor prognosis in PitNET patients. Conclusions Our data and analysis manifested the basic cell types in the normal pituitary and inherent heterogeneity of PitNETs, identified several features of the tumor immune microenvironments, and found a novel epithelial cell sub-population with aggressive signatures across all the studied cases.https://doi.org/10.1186/s13073-023-01267-3Pituitary neuroendocrine tumorTumor heterogeneityTumor microenvironmentSingle-cell RNA sequencing |
| spellingShingle | Nan Yan Weiyan Xie Dongfang Wang Qiuyue Fang Jing Guo Yiyuan Chen Xinqi Li Lei Gong Jialin Wang Wenbo Guo Xuegong Zhang Yazhuo Zhang Jin Gu Chuzhong Li Single-cell transcriptomic analysis reveals tumor cell heterogeneity and immune microenvironment features of pituitary neuroendocrine tumors Genome Medicine Pituitary neuroendocrine tumor Tumor heterogeneity Tumor microenvironment Single-cell RNA sequencing |
| title | Single-cell transcriptomic analysis reveals tumor cell heterogeneity and immune microenvironment features of pituitary neuroendocrine tumors |
| title_full | Single-cell transcriptomic analysis reveals tumor cell heterogeneity and immune microenvironment features of pituitary neuroendocrine tumors |
| title_fullStr | Single-cell transcriptomic analysis reveals tumor cell heterogeneity and immune microenvironment features of pituitary neuroendocrine tumors |
| title_full_unstemmed | Single-cell transcriptomic analysis reveals tumor cell heterogeneity and immune microenvironment features of pituitary neuroendocrine tumors |
| title_short | Single-cell transcriptomic analysis reveals tumor cell heterogeneity and immune microenvironment features of pituitary neuroendocrine tumors |
| title_sort | single cell transcriptomic analysis reveals tumor cell heterogeneity and immune microenvironment features of pituitary neuroendocrine tumors |
| topic | Pituitary neuroendocrine tumor Tumor heterogeneity Tumor microenvironment Single-cell RNA sequencing |
| url | https://doi.org/10.1186/s13073-023-01267-3 |
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