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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: Wang, Feiyang, Jia, Wentong, Fan, Mengjie, Shao, Xuan, Li, Zhilang, Liu, Yongjie, Ma, Yeling, Li, Yu-Xia, Li, Rong, Tu, Qiang, Wang, Yan-Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602400/
https://www.ncbi.nlm.nih.gov/pubmed/33482359
http://dx.doi.org/10.1016/j.gpb.2020.11.002
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author Wang, Feiyang
Jia, Wentong
Fan, Mengjie
Shao, Xuan
Li, Zhilang
Liu, Yongjie
Ma, Yeling
Li, Yu-Xia
Li, Rong
Tu, Qiang
Wang, Yan-Ling
author_facet Wang, Feiyang
Jia, Wentong
Fan, Mengjie
Shao, Xuan
Li, Zhilang
Liu, Yongjie
Ma, Yeling
Li, Yu-Xia
Li, Rong
Tu, Qiang
Wang, Yan-Ling
author_sort Wang, Feiyang
collection PubMed
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.
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spelling pubmed-86024002021-11-23 Single-cell Immune Landscape of Human Recurrent Miscarriage Wang, Feiyang Jia, Wentong Fan, Mengjie Shao, Xuan Li, Zhilang Liu, Yongjie Ma, Yeling Li, Yu-Xia Li, Rong Tu, Qiang Wang, Yan-Ling Genomics Proteomics Bioinformatics Original Research 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. Elsevier 2021-04 2021-01-19 /pmc/articles/PMC8602400/ /pubmed/33482359 http://dx.doi.org/10.1016/j.gpb.2020.11.002 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Wang, Feiyang
Jia, Wentong
Fan, Mengjie
Shao, Xuan
Li, Zhilang
Liu, Yongjie
Ma, Yeling
Li, Yu-Xia
Li, Rong
Tu, Qiang
Wang, Yan-Ling
Single-cell Immune Landscape of Human Recurrent Miscarriage
title 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_short Single-cell Immune Landscape of Human Recurrent Miscarriage
title_sort single-cell immune landscape of human recurrent miscarriage
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602400/
https://www.ncbi.nlm.nih.gov/pubmed/33482359
http://dx.doi.org/10.1016/j.gpb.2020.11.002
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