基于单细胞多组学解析生长激素腺瘤的转录-翻译解偶联机制OA

Objective To investigate the transcriptomic and translatomic heterogeneity of sparsely granulated som-atotroph 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 sub-populations 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.Cyto-TRACE analysis indicated that low different ion state of some tumor subpopulations significantly down-regulated ri-bosome biogenesis and translation pathways while up-regulated OXPHOS and autophagy-related pathways,sug-gesting that the inhibition of translational activity might be closely related to the maintenance of a poorly differenti-ated 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 undifferenti-ated 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.