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Author Spotlight: Modeling an Aspect of Preeclampsia in Female Mice Using Hypoxic Human Placenta-Derived Small Extracellular Vesicles
Published on: January 26, 2024
Maternal-Fetal Interface Cell Dysfunction in Patients With Preeclampsia Revealed via Single-Cell RNA Sequencing
Songyuan Xiao1, Yiling Ding1, Ling Yu1
1Department of Obstetrics and Gynecology, Second XiangYa Hospital of Central South University, Changsha, Hunan, China.
Insights
Preeclampsia (PE) is linked to abnormal placental cell differentiation and impaired immune responses. Specifically, villous cytotrophoblasts (VCT) differentiate towards syncytiotrophoblasts (SCT) instead of extravillous trophoblasts (EVT), and T-cell differentiation is altered, impacting pregnancy health.
Area of Science:
- Reproductive biology
- Immunology
- Genomics
Background:
- Preeclampsia (PE) is a major cause of maternal and fetal mortality.
- Placental and decidual cell dysfunction are implicated in PE pathogenesis.
- The precise mechanisms underlying PE remain unclear.
Purpose of the Study:
- Investigate heterogeneous cell type changes in placental and decidual tissues from PE patients.
- Utilize single-cell sequencing to analyze cellular alterations in PE.
- Elucidate the role of specific cell types in PE development.
Main Methods:
- Single-cell RNA sequencing of placental and decidual tissues from PE (n=3) and normal pregnancy (NP) (n=3) cohorts.
- Analysis of 32,279 cells across nine identified cell types, including trophoblasts and immune cells.
- Gene set variation analysis (GSVA), cell-reclustering, and pseudotime analysis to assess cell differentiation and function.
Main Results:
- Villous cytotrophoblasts (VCT) in PE exhibited altered differentiation towards syncytiotrophoblasts (SCT) instead of extravillous trophoblasts (EVT).
- The invasive potential of PE extravillous trophoblast (EVT) cells was reduced due to decreased expression of TMEM200A.
- An impaired immune microenvironment was observed, characterized by altered T-cell differentiation favoring regulatory T cells (Treg) over CD8+ T cells.
Conclusions:
- Understanding T-cell differentiation and its influence on VCT differentiation is critical for PE pathogenesis.
- Altered immune cell dynamics, particularly T-cell subsets, play a significant role in PE.
- Aberrant trophoblast differentiation contributes to the pathophysiology of preeclampsia.
Problem:
Preeclampsia (PE) is a leading cause of perinatal maternal and fetal mortality. Clinical and pathological studies suggest that placental and decidual cell dysfunction may contribute to this condition. However, the pathogenesis of PE remains poorly understood. Therefore, this study aims to investigate the heterogeneous changes in cell types within placental and decidual tissue isolated from cesarean sections using single-cell sequencing.
Method Of Study:
Patients included those diagnosed with PE (n = 3) and normal pregnancy (NP) (n = 3). Overall, 32 279 cells (PE: 16.575; NP: 15 704) were identified across nine cell types, including villous cytotrophoblast (VCT), syncytiotrophoblast (SCT), extravillous trophoblasts (EVT), endothelial cells, neutrophil, Hofbauer cells, T cells, dendritic cells (DC), macrophages, fibroblasts, and B cells. VCT and T cells subclusters and pseudotime were analyzed. The in vivo and in vitro experiments are focused on the invasion ability of EVT.
Results:
Using gene set variation analysis (GSVA) for differential expression genes, cell-reclustering, and pseudotime analysis, the VCT in patients with PE showed a tendency to differentiate toward SCT instead of EVT. And the invasive ability of PE EVT cells was declined by decreased expression of the invasion-related gene TMEM200A. Additionally, the impaired immune environment of T-cell differentiation into CD8+T cells instead of Treg cells is the main change related to PE.
Conclusions:
These findings suggest that understanding how T cell differentiation occurs in the early stage of pregnancy and how the predominantly CD8+T cell-driven immune environment influences VCT differentiation are crucial for elucidating the pathogenesis of PE.
