Searching for the influencers among placental immune cells in preeclampsia.
It has been posited that cells of the maternal and fetal immune systems communicate to lead to immune tolerance during pregnancy however been inconclusive. Here, we profiled single-cell transcriptional signatures by placental layers consisting of maternal-fetal interface (MF) and deep-placenta (Pla) regions, then searched influencer gene for preeclampsia (PE). As underpin principle of the failure of immune tolerance, we start by clarifying the systemic framework, which consists of immune interactions frequency (IIF) and specific trigger (i.e., influencer) tolerance (IT) models. We elaborate single-cell transcriptional profiles of normal term (Norm) and preeclampsia preterm parturitions (PePT). Fetal and maternal cells admixed across placenta, in both of Norms and PePTs, rejecting IIF model of immune failure of pregnancy posed by exceed interactions of fetomaternal cells. Whereases placental layers are well mixed with maternal cells, we identified conserved gradual immune transition of fetal T cells in both of PePT and Norm, disapproving IIF model. To search the influencer of PePT in IT model, we established and validated a classification model for PePT and Norm immune cells including T cells, then prioritized major contributors for classifier model. Interestingly, those prioritized genes are highly enriched with ligands and receptors (p-value 5.98e-05). Out of prioritized ligand-receptors, SPP1 and CD44 suggested as influencer of inflammation signatures and experimentally validated by exclusive colocalization of SPP1 and CD44 expressed cells in placentas of PePT. Different IL4 and IFN-g levels in the serum and urine of PePTs further support contribution of SPP1 in associated pathways, including allograft rjection pathway. Collectively, our finding provide insight into the influence of specific immune interactions between cells in human placenta and these influencer-derived impact the immune harmonization of PePT. Overall design: Following elective cesarean delivery, placental tissues were collected from the maternal-fetal interface and deep-placenta of women with term birth (Norm, =37 weeks) or preeclampsia-associated preterm birth (PePT, =34 weeks). These tissues were freshly isolated, dissociated into single-cell suspensions, and subjected to scRNA-seq analysis.