Article
Single-cell transcriptome analysis of gonadotroph pituitary adenoma indicates interaction between fibroblasts and tumour cells with stem cell characteristics
Einzelzelltranskriptomanalyse von gonadotrophen Hypophysenadenomen deutet auf Interaktion zwischen Fibroblasten und Tumorzellen mit Stammzelleigenschaften hin
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Published: | May 25, 2022 |
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Objective: Patients with gonadotroph pituitary adenoma have a good overall survival, but high morbidity if the tumor is not completely resectable due to tumor regrowth and mass effects. Mechanisms of tumor progression are largely unknown and the impact of cellular interactions between the tumor microenvironment (TME) and tumor cells have not been studied. In this project we aim to unravel how infiltrating cells influence the tumor cell progression versus induction of cellular senescence. Insights into these mechanisms of cellular communication might result in innovative target-directed therapeutical approaches.
Methods: Single-cell RNA sequencing was performed for 17,254 individual cells from fresh tumor samples of gonadotroph subtype obtained from 7 patients with pituitary adenoma through transsphenoidal surgery. Subsequent analyses included differential gene expression profiling of distinct subpopulations of cells and their ligand-receptor (L-R) interactions.
Results: Unsupervised clustering analysis identified nearly 62% of cells as TME, including macrophage/microglia, NK-/T-cells, fibroblasts/pericytes and endothelial cells. In addition to the known activation of the MAPK signaling pathway, putative tumor cells (PTC) show an high intratumoral heterogenity, e. g. with stem cells characteristics or epithelial cell differentiation for individual clusters. L-R interaction analysis indicates extensive crosstalk between fibroblasts/pericytes and a PTC cluster that exhibits stem cell properties, and these interactions are enriched in components of the Notch, Hippo and TGF-beta signaling pathways.
Conclusion: Our single-cell transcriptome analysis unravel cellular heterogeneity and cellular communications in gonadotroph pituitary adenoma. In addition we provide novel preliminary insights into the interaction of gonadotroph pituitary adenoma cells with their microenvironnement and how infiltrating cells might impact cellular differentiation within these tumors.