Single-cell Immune Landscape of Human Recurrent Miscarriage
- Author:
Wang FEIYANG
1
,
2
,
3
;
Jia WENTONG
;
Fan MENGJIE
;
Shao XUAN
;
Li ZHILANG
;
Liu YONGJIE
;
Ma YELING
;
Li YU-XIA
;
Li RONG
;
Tu QIANG
;
Wang YAN-LING
Author Information
1. State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China
2. Beijing Institute of Stem Cell and Regenerative Medicine,Beijing 100101,China
3. University of Chinese Academy of Sciences,Beijing 101408,China
- Keywords:
Decidual and peripheral leukocytes;
Single-cell RNA-sequencing;
Recurrent miscarriage;
Early pregnancy;
Developmental trajectory
- From:
Genomics, Proteomics & Bioinformatics
2021;19(2):208-222
- CountryChina
- Language:Chinese
-
Abstract:
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 asso-ciated with adverse pregnancy outcomes including recurrent miscarriage (RM).However,an in-depth 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 unex-plained 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 interac-tions 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 com-prehensive 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.
