单细胞RNA测序揭示妊娠期糖尿病对胎儿单核细胞的不良影响。

Adverse effects of gestational diabetes mellitus on fetal monocytes revealed by single-cell RNA sequencing.

作者信息

Yin Min, Zhang Yan, Li Xinyu, Liu Shanshan, Huang Juan, Yu Haibo, Li Xia

机构信息

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

Section of Endocrinology, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.

出版信息

iScience. 2023 Dec 5;27(1):108637. doi: 10.1016/j.isci.2023.108637. eCollection 2024 Jan 19.

DOI:10.1016/j.isci.2023.108637

PMID:38188508

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10770529/

Abstract

Gestational diabetes mellitus (GDM), the most prevalent metabolic disorder during pregnancy, has long-term risks of metabolic diseases in offspring. However, the underlying mechanisms remain unclear. Here, we analyzed single-cell transcriptional data of cord blood mononuclear cells (CBMCs) from fetuses of healthy and GDM mothers, peripheral blood mononuclear cells from children and adolescents, and coronary plaques myeloid cells from atherosclerosis. Our results demonstrated that monocytes in cord blood were characterized with down-regulated proinflammatory-related pathways and up-regulated proliferation-related pathways. And monocytes in cord blood from GDM mothers were featured with expanded CXCL8+IL1B+ subclusters, enhanced crosstalk with neutrophil granulocytes and augmented adhesive and phagocytic abilities. Interestingly, CXCL8+IL1B+ monocytes influenced by GDM had transcriptome similarity with those of coronary plaques myeloid cells from individuals with atherosclerotic cardiovascular disease. Collectively, our data reveal adverse impact of maternal GDM environment on fetal monocytes and propose potential mechanisms between maternal GDM and offspring atherosclerosis.

摘要

妊娠期糖尿病（GDM）是孕期最常见的代谢紊乱疾病，会给后代带来代谢性疾病的长期风险。然而，其潜在机制仍不清楚。在此，我们分析了来自健康母亲和患有GDM母亲胎儿的脐带血单个核细胞（CBMC）、儿童和青少年外周血单个核细胞以及动脉粥样硬化冠状动脉斑块髓样细胞的单细胞转录数据。我们的结果表明，脐带血中的单核细胞具有促炎相关通路下调和增殖相关通路上调的特征。并且，来自患有GDM母亲的脐带血中的单核细胞具有CXCL8+IL1B+亚群扩大、与中性粒细胞的串扰增强以及黏附和吞噬能力增强的特点。有趣的是，受GDM影响的CXCL8+IL1B+单核细胞与患有动脉粥样硬化性心血管疾病个体的冠状动脉斑块髓样细胞具有转录组相似性。总体而言，我们的数据揭示了母亲GDM环境对胎儿单核细胞的不利影响，并提出了母亲GDM与后代动脉粥样硬化之间的潜在机制。