GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296667/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296667GEOGSEfalselncRNA-operated stem cell fate control: RPS3 organizes the in situ Gm16751-Zhx3 interactome to program spermatogonial differentiation [Long RNA-Seq]Long non-coding RNAs (lncRNAs) play pivotal regulatory roles in mammalian male gametogenesis. Advances in high-throughput technologies have demonstrated that lncRNAs orchestrate robust, flexible, and context-specific gene regulatory networks through dynamic interactions with proteins, DNA, and RNA, modulating transcriptional and post-transcriptional processes. However, the mechanistic role of in situ lncRNA-mRNA interactions in spermatogonial stem cell (SSC) differentiation remains poorly understood. In this study, we employed RIC-seq (RNA in situ conformation sequencing) and LongRNA-seq to systematically identify a functional interaction between lncRNA Gm16751 and Zhx3 mRNA during SSC differentiation, which was further visualized via a Circos plot. Mechanistically, we demonstrated that Gm16751 enhances the mRNA stability of Zhx3, thereby promoting SSC differentiation. Furthermore, mass spectrometry analysis revealed that RPS3 (Ribosomal Protein S3) serves as a critical RNA-binding protein (RBP) that bridges the interaction between Gm16751 and Zhx3, ultimately stabilizing Zhx3 mRNA and modulating SSC differentiation. Our findings provide novel mechanistic insights into the lncRNA-mRNA regulatory axis in SSC differentiation and establish a foundation for understanding the molecular etiology of male germ cell developmental disorders and spermatogenic dysfunction.2026/06/10GSE296667GSM8974394GSM8974393GSM8974396GSM897439524247296667Mus musculus[42231399]