关键词: 生长激素腺瘤, 稀疏颗粒型, 单细胞转录组测序, 单细胞(翻译组)核糖体印迹测序, 翻译效率

Abstract: Objective To investigate the transcriptomic and translatomic heterogeneity of sparsely granulated somatotroph tumor (SGST) and to elucidate the synergistic mechanisms of gene expression at the transcriptional and translational level. Methods Single-cell RNA sequencing (scRNA-seq) and single-cell ribosome sequencing(scRibo-seq) were performed on tumor tissue samples from one patient with SGST. Dimensionality reduction and clustering were utilized to identify cell subpopulations. The CytoTRACE algorithm was applied to assess cell differ- entiation states. By comparing gene expression at both RNA and translational level, the transcriptional-translational association characteristics of invasion-related genes were explored. Results Three distinct cell subpopulations were identified, including tumor cells, pericytes, and endothelial cells, with tumor cells accounting for 94.9%. The tumor cells exhibited high heterogeneity and could be further subdivided into distinct functional states, including “proliferative” “oxidative phosphorylation(OXPHOS)” and “pituitary-like” subtypes. CytoTRACE analysis indicated that low different ion state of some tumor subpopulations significantly down-regulated ribosome biogenesis and translation pathways while up-regulated OXPHOS and autophagy-related pathways, suggesting that the inhibition of translational activity might be closely related to the maintenance of a poorly differentiated tumor state. Integrated analysis revealed a significant transcriptional-translational uncoupling: Key invasion genes such as MMP1 and SNAI2 showed low transcriptional levels but significantly elevated translation efficiency. Conversely, ribosome-related genes exhibited low translation efficiency. Conclusions SGST possesses significant transcriptomic heterogeneity, where subpopulations of low differention maintain a hypometabolic and undifferentiated state by suppressing ribosome biogenesis. Rather than relying on transcriptional abundance, tumor cells drive a rapid synthesis of invasion-related proteins by specifically enhancing translation efficiency. This reveals a key post-transcriptional regulatory mechanism underlying the invasive growth of SGST.

Key words: somatotroph adenoma, sparsely granulated, single-cell RNA sequencing, single-cell ribosome sequencing, translation efficiency