复发性流产滋养细胞的单细胞转录组图谱:亚型与功能失调研究OA

Objective:To investigate the aberrant states of trophoblast subpopulations in patients with recurrent spontaneous abortion(RSA)through analysis of single-cell transcrip-tomic data and to identify key genes,thereby providing a theoretical foundation for understand-ing the pathogenesis and progression of RSA.Methods:Single-cell RNA sequencing data(GSE214)meeting the criteria were downloaded from the Gene Expression Omnibus(GEO)database.Quality control and standardized analysis were performed using the Seurat pipeline,followed by manual annotation of cell types.Trophoblasts were extracted for trajectory inference,cell-cell communication analysis,and differential gene expression analysis.Transcription factor(TF)analysis was conducted to identify key regulators in RSA.Functional validation of the i-dentified TF was performed through cellular experiments to assess its impact on trophoblast be-havior.Results:Trophoblast subpopulations in RSA exhibit a distinct disproportion,show differ-entiation arrest,and demonstrate functional dysregulation.The mTORC1 signaling pathway is significantly downregulated in RSA trophoblasts.Adaptation to physiological hypoxia is im-paired.Transcription factor analysis identified interleukin enhancer binding factor 2(ILF2)as a key regulator of trophoblast function.Knockdown of ILF2 significantly inhibited trophoblast proliferation,invasion,and migration.Conclusion:The downregulation of the mTORC1 signaling pathway mediates impaired adaptation to physiological hypoxia.This impairment serves as the core mechanism for trophoblast dysfunction in RSA.Trophoblast function is likely regulated by ILF2 through the mTORC1 signaling axis.A theoretical foundation for the development of diag-nostic and therapeutic targets for RSA is established by these findings.