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Single-cell Immune Landscape of Human Recurrent Miscarriage

Genomics, Proteomics & Bioinformatics 2021年第2期19卷 208-222页

作者： Feiyang Wang Wentong Jia Mengjie Fan Xuan Shao Zhilang Li Yongjie Liu Yeling Ma Yu-Xia Li Rong Li Qiang Tu Yan-Ling Wang State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China National Clinical Center for Obstetrics and Gynecology Peking University Third HospitalBeijing 100191China State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyInnovation Academy for Seed DesignChinese Academy of SciencesBeijing 100101China Beijing Institute of Stem Cell and Regenerative Medicine Beijing 100101China University of Chinese Academy of Sciences Beijing 101408China

t Successful pregnancy in placental mammals substantially depends on the establishment of maternal immune tolerance to the semi-allogenic fetus.Disorders in this process are tightly associated with adverse pregnancy outcomes including recurrent miscarriage(RM).However,an indepth understanding of the systematic and decidual immune environment in RM remains largely lacking.In this study,we utilized single-cell RNA-sequencing(scRNA-seq)to comparably analyze the cellular and molecular signatures of decidual and peripheral leukocytes in normal and unexplained RM pregnancies at the early stage of gestation.Integrative analysis identifies 22 distinct cell clusters in total,and a dramatic difference in leukocyte subsets and molecular properties in RM cases is revealed.Specifically,the cytotoxic properties of CD8^(+)effector T cells,nature killer(NK),and mucosal-associated invariant T(MAIT)cells in peripheral blood indicates apparently enhanced pro-inflammatory status,and the population proportions and ligand–receptor interactions of the decidual leukocyte subsets demonstrate preferential immune activation in RM patients.The molecular features,spatial distribution,and the developmental trajectories of five decidual NK(dNK)subsets have been elaborately illustrated.In RM patients,a dNK subset that supports embryonic growth is diminished in proportion,while the ratio of another dNK subset with cyto toxic and immune-active signature is significantly increased.Notably,a unique pro-inflammatory CD56^(+)CD16^(+)dNK subset substantially accumulates in RM decidua.These findings reveal a comprehensive cellular and molecular atlas of decidual and peripheral leukocytes in human early pregnancy and provide an in-depth insight into the immune pathogenesis for early pregnancy loss.

关键词： decidual and peripheral leukocytes Single-cell RNA-sequencing Recurrent miscarriage Early pregnancy Developmental trajectory

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