Single-cell RNA Sequencing Deciphers Immune Landscape of Human Recurrent Miscarriage

Introduction Pregnancy is a mysterious biological process that presents great challenges to the maternal immune system.In the early 1950s,the‘‘fetal allograft”concept was described for the first time by Peter Medawar,and the unique immunology of the maternal-fetal interface was recognized[1].Correct and precise interaction between mother and fetus plays an important role during pregnancy process,such as the apposition,adhesion,implantation,and growth of embryo in uterus[2].In 1991,Colbern and Main proposed that the maternal immune cells directly interact with placenta but not the fetus[3].Therefore,information concerning the cross-talk between maternal immune cells and placenta during normal pregnancy will provide clues to explore the underlying mechanism of pathological pregnancy.Immune cells,such as natural killer(NK),macrophage,T,and dendritic cells,have been demonstrated to play important roles during normal pregnancy[4].With the development of single-cell RNA sequencing(scRNA-seq)technologies,researchers are devoted to providing a whole picture about the immune cellular composition and inter-cellular communication events during normal pregnancy[5,6].These foundational studies reveal that immune cell subsets,which are classified based on different markers at high resolution,exert specific function during pregnancy establishment.However,the panoramic analysis of immune subsets at high resolution in pathological pregnancy remains lacking.