Single-cell transcriptome and genome analyses of pituitary neuroendocrine tumors.
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ABSTRACT: Background
Pituitary neuroendocrine tumors (PitNETs) are the second most common intracranial tumor. We lacked a comprehensive understanding of the pathogenesis and heterogeneity of these tumors.Methods
We performed high-precision single-cell RNA sequencing for 2,679 individual cells obtained from 23 surgically resected samples of the major subtypes of PitNETs from 21 patients. We also performed single-cell multi-omics sequencing for 238 cells from 5 patients.Results
Unsupervised clustering analysis distinguished all tumor subtypes, which was in accordance with the classification based on immunohistochemistry and provided additional information. We identified three normal endocrine cell types: somatotrophs, lactotrophs and gonadotrophs. Comparisons of tumor and matched normal cells showed that differentially expressed genes of gonadotroph tumors were predominantly downregulated, while those of somatotroph and lactrotroph tumors were mainly upregulated. We identified novel tumor-related genes, such as AMIGO2, ZFP36, BTG1 and DLG5. Tumors expressing multiple hormone genes showed little transcriptomic heterogeneity. Furthermore, single-cell multi-omics analysis demonstrated that the tumor shad a relatively uniform pattern of genome with slight heterogeneity in copy number variations.Conclusions
Our single-cell transcriptome and single-cell multi-omics analyses provide novel insights into the characteristics and heterogeneity of these complex neoplasms for the identification of biomarkers and therapeutic targets.
SUBMITTER: Cui Y
PROVIDER: S-EPMC8563320 | biostudies-literature |
REPOSITORIES: biostudies-literature
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