Immune cell profiling of preeclamptic pregnant and postpartum women by single-cell RNA sequencing

Abstract

Preeclampsia (PE), a leading cause of maternal and fetal morbidity and mortality, is closely related to the immune system alterations. However, little is known about the landscape and heterogeneity of maternal immune system at single-cell level among PE patients. In this study, peripheral blood mononuclear cells (PBMCs) were isolated from three early-onset preeclamptic pregnant women and two healthy control, respectively. Single-cell RNA sequencing was performed on 10× genomics platform and single-cell transcriptomes were obtained to characterize immune cell subgroups at the pregnant and postpartum stages. In total, 80,429 single-cell transcriptomes were obtained. 19 cellular compositions were identified, which were categorized into six cell types including T cells, natural killer (NK) cells, B cells, monocytes, plasmacytoid dendritic cells and conventional dendritic cells. There were excessive activation of B cells, monocytes and NK cells in PE patients at the pregnant stage based on comparative analysis. Lower immune response activation was noticed in CD4⁺ and CD8⁺ T cells in PE patients, especially the low-activation of memory T cells at the pregnant and postpartum stages. PE patients showed high activation of B cells in pregnancy persisted postpartum and lower activation of memory T cells, indicating their persistent effects on the pathogenesis and recurrence risk of PE. This study provide a broad characterization of the single-cell transcriptome of PBMCs in PE, which contributes to identification of immune imbalance for its monitoring and treatment.

PLAIN LANGUAGE SUMMARY

Preeclampsia (PE) is characterized by de novo onset of proteinuria or other maternal organ dysfunction and hypertension at gestational age of 20 weeks or more. Its pathogenesis is associated with the abnormal placental development caused by insufficient trophoblast invasion and impaired spiral artery remodeling, and consequent maternal-inflammatory response and endovascular dysfunction. Peripheral immune response may play a crucial role in the pathogenesis of PE. Besides, lower activation of CD4⁺ memory T cells was related to the onset of PE. However, the roles of the immune cells in PE recurrence are still not well defined. Single-cell RNA sequencing was performed to immune cells in PE patients, which confirmed an excessive inflammatory state in monocytes, NK cells and B cells and lower activation of memory T cells in PE women. Our data showed that PE was associated with the immune imbalance, which may provide potential therapeutic strategies for its treatment.

Keywords:

• Hypertension
• immune response
• Preeclampsia
• pregnancy
• single-cell RNA sequencing

Authors’ contributions

JH, QG wrote the manuscript. JH, CL and YR contributed to the sample collection from patients. QG and QY performed the experiment. YW analyzed the Data. QL prepared the Figures and Tables. YL and JL designed the research. All authors contributed to the article and approved the submitted version.

Disclosure of interest

QG, QY, YW, QL and YL are employees of Berry Genomics. The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethics approval and consent to participate

The studies involving human participants were reviewed and approved by Ethics Committee of Peking Union Medical College Hospital (No. ZS-2694). Written informed consent was obtained from each participant.

Data availability statement

The sequencing data has been deposited in the NCBI GEO database (https://www.ncbi.nlm.nih.gov/geo/; accession number: GSE192693).

Additional information

Funding

This work was supported by the Beijing Municipal Natural Science Foundation under Grant No. 7212072; and the National Key Research and Development Program of China under Grant No. 2019YFC1005105.