Placenta accreta spectrum disorder at single cell resolution: a loss of boundary limits in the uterine endothelium and decidua.
Objective: The objective of this study is to utilize advances in single-cell RNAsequencing to characterize cellular heterogeneity and transcriptomic signatures of PAS. Our findings can elucidate mechanisms of abnormal placental invasion and identify targets for potential diagnostic and therapeutic biomarkers of PAS. Results: Placental samples from PAS participants and non-PAS cesarean births were included. In total, we analyzed 31,406 individual cells expressing an average of 1,493 genes. Clustering analysis of gene expression identified multiple populations of cells representing syncytiotrophoblasts, cytotrophoblasts, extravillous trophoblasts, decidua,endothelial cells, myeloid, natural killer, and lymphoid cells. When analyzed by disease phenotype, AI showed a unique gene signature most prominently in the endothelial population. The highest expression in AI compared to AO and C was seen in the following genes: DLK1, EGFL6, HGF, APOLD1, and EDNRB. Gene set enrichment analysis of AI endothelial cells identified the following key pathways: blood vessel development, response to growth factors and hormones, regulation of cell adhesion and migration, and pathways in cancer. Conclusions: We present a comprehensive single-cell atlas of PAS across the site of invasion and site of non-adherence. By integrating expression from individual genes per cell, we identified endothelial cells as a key subpopulation in invasive accreta, with expression of genes involved in multiple angiogenic, growth, and mechanical-signaling pathways. After validation, these gene targets may be used to refine diagnostic assays for placenta accreta in early gestation, track disease progression over time, and inform Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation therapeutic discoveries. Overall design: Study Design: We generated a single-cell atlas of gene expression at the site of accreta invasion (AI) versus site of accreta opposite, non-invasion (AO) in PAS placentas versus controls (C). Mechanical and enzymatic dissociation of single cell suspensions of placentas was performed with confirmation of high cell viability and RNA quality prior to library creation. We utilized a high-throughput whole-transcriptome system for single-cell sequencing.