Single-cell Immune Landscape of Human Recurrent Miscarriage

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 in-depth understanding of...

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Autores principales:	Feiyang Wang, Wentong Jia, Mengjie Fan, Xuan Shao, Zhilang Li, Yongjie Liu, Yeling Ma, Yu-Xia Li, Rong Li, Qiang Tu, Yan-Ling Wang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Decidual and peripheral leukocytes Single-cell RNA-sequencing Recurrent miscarriage Early pregnancy Developmental trajectory Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/fb619ef6a70444ebb02f3c91a8f1af31
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spelling	oai:doaj.org-article:fb619ef6a70444ebb02f3c91a8f1af312021-11-16T04:09:21ZSingle-cell Immune Landscape of Human Recurrent Miscarriage1672-022910.1016/j.gpb.2020.11.002https://doaj.org/article/fb619ef6a70444ebb02f3c91a8f1af312021-04-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1672022921000036https://doaj.org/toc/1672-0229Successful 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 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 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 cytotoxic 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.Feiyang WangWentong JiaMengjie FanXuan ShaoZhilang LiYongjie LiuYeling MaYu-Xia LiRong LiQiang TuYan-Ling WangElsevierarticleDecidual and peripheral leukocytesSingle-cell RNA-sequencingRecurrent miscarriageEarly pregnancyDevelopmental trajectoryBiology (General)QH301-705.5ENGenomics, Proteomics & Bioinformatics, Vol 19, Iss 2, Pp 208-222 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Decidual and peripheral leukocytes Single-cell RNA-sequencing Recurrent miscarriage Early pregnancy Developmental trajectory Biology (General) QH301-705.5
spellingShingle	Decidual and peripheral leukocytes Single-cell RNA-sequencing Recurrent miscarriage Early pregnancy Developmental trajectory Biology (General) QH301-705.5 Feiyang Wang Wentong Jia Mengjie Fan Xuan Shao Zhilang Li Yongjie Liu Yeling Ma Yu-Xia Li Rong Li Qiang Tu Yan-Ling Wang Single-cell Immune Landscape of Human Recurrent Miscarriage
description	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 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 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 cytotoxic 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.
format	article
author	Feiyang Wang Wentong Jia Mengjie Fan Xuan Shao Zhilang Li Yongjie Liu Yeling Ma Yu-Xia Li Rong Li Qiang Tu Yan-Ling Wang
author_facet	Feiyang Wang Wentong Jia Mengjie Fan Xuan Shao Zhilang Li Yongjie Liu Yeling Ma Yu-Xia Li Rong Li Qiang Tu Yan-Ling Wang
author_sort	Feiyang Wang
title	Single-cell Immune Landscape of Human Recurrent Miscarriage
title_short	Single-cell Immune Landscape of Human Recurrent Miscarriage
title_full	Single-cell Immune Landscape of Human Recurrent Miscarriage
title_fullStr	Single-cell Immune Landscape of Human Recurrent Miscarriage
title_full_unstemmed	Single-cell Immune Landscape of Human Recurrent Miscarriage
title_sort	single-cell immune landscape of human recurrent miscarriage
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/fb619ef6a70444ebb02f3c91a8f1af31
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Single-cell Immune Landscape of Human Recurrent Miscarriage

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