SOX4 Mediated Differentiation of Specific T Lymphocyte Subsets at the Maternal-Fetal Interface Contributes to Preterm Labor [RNA-Seq]

Preterm labor is one of the most common pregnancy complications and the leading cause of perinatal neonatal mortality, and its prevention and treatment strongly rely on the depiction of mechanisms underlying the initiation of labor. T lymphocyte are major players of the adaptive immune system and balance tolerance and protection at the maternal-fetal interface. Here we integrated single-cell RNA sequencing and single-cell ATAC sequencing analyses of human decidua basalis and decidua parietalis from term and preterm labor to depict the composition of T cells at the maternal-fetal interface during late pregnancy. Our research identified CD8-naïve-SOX4 subset associated with preterm labor, which showed a significant decrease of proportion in the basalis decidua of preterm labor. The transcription factor SOX4 was specifically expressed in naïve CD8+ T cells and was significantly downregulated in the CD8-naïve-SOX4 subset in the decidua basalis of preterm labor. Mechanically, SOX4 plays a pivotal role in mediating T cell differentiation and promotes the differentiation of naïve CD8+ T cells into effector CD8+ T cells in the preterm labor based on pseudotime analysis. We generated a co-culture system to simulate cellular interactions between T cells and uterine smooth muscle cells or amniotic epithelial cells at the maternal-fetal interface, and RNA-sequencing analysis of myometrial cells and amniotic epithelial cells co-cultured with SOX4-deficient T cells revealed disruption of actin filament assembly in uterine smooth muscle cells and F-actin rearrangement in amniotic epithelial cells.