Integrated Analysis of WES and scRNA-Seq Data Reveals the Genetic Basis of Immune Dysregulation in Unexplained Recurrent Pregnancy Loss

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis Pub Date : 2025-03-11 DOI:10.1002/jcla.70011

Zhao-Jing Lin, Lei Zhu, Yi Dong, Jiao Yun, Ya-Nan Zhi, Wei Zhang, Yan-Mei Sun, Yu-Jie Jiang, Shu Liu, Liang-Liang Fan, Ya-Li Li, Shuai Guo

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引用次数: 0

Abstract

Objective

This study aimed to identify genetic variants and their functional consequences underlying Unexplained Recurrent Pregnancy Loss (uRPL) through comprehensive genomic and transcriptomic analyses.

Methods

We recruited 13 Chinese uRPL patients and performed Whole Exome Sequencing (WES) on chorionic villi samples from miscarriage tissues. Additionally, we conducted an integrative analysis using single-cell RNA sequencing data from decidual immune cells to examine expression patterns.

Results

WES analysis pinpointed variants in the four MUC genes (MUC4, MUC6, MUC16, and MUC17), six lipid metabolism genes in immune cells (ABCA4, ABCA7, ABCB5, ABCC8, ADGRV1, and ANK3), and two structural genes (PIEZO1 and PKD1), whose variants impair mucosal barriers and lipid homeostasis, thereby leading to immune dysregulation and contributing to uRPL. To delve deeper into the effects of these genetic variants on cellular expression patterns, we undertook an integrative analysis using a single-cell dataset from decidual immune cells in uRPL cases. We observed significant dysregulation of lipid metabolism within immune cells, reduced heat shock protein expression, and enhanced chemokine signaling in uRPL samples, indicating a pro-inflammatory state.

Conclusions

In summary, our study reveals a complex interplay between genetic variants and immune cell dysfunctions in uRPL, emphasizing the role of identified genetic variants in driving pro-inflammatory states. These findings provide a comprehensive view of the molecular mechanisms underlying uRPL, opening paths for novel therapeutic interventions and improved clinical management.

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来源期刊

Journal of Clinical Laboratory Analysis 医学-医学实验技术

CiteScore

5.60

自引率

7.40%

发文量

584

审稿时长

6-12 weeks

期刊介绍： Journal of Clinical Laboratory Analysis publishes original articles on newly developing modes of technology and laboratory assays, with emphasis on their application in current and future clinical laboratory testing. This includes reports from the following fields: immunochemistry and toxicology, hematology and hematopathology, immunopathology, molecular diagnostics, microbiology, genetic testing, immunohematology, and clinical chemistry.