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Single-cell insights into trophoblast heterogeneity and adaptive dysfunction in selective fetal growth restriction

GSE314816 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2026/01/06 Platform GPL24676
Summary
Selective fetal growth restriction (sFGR) in monochorionic twins reflects placental dysfunction, but trophoblast adaptation mechanisms remain unclear. Using single-cell RNA sequencing of three MCDA twin pairs, we reveal villous cytotrophoblasts (VCT) in growth-restricted placentas shift from TP63/SOX6-expressing barrier phenotypes to metabolically stressed YY1/RELA-activated states, with upregulated glycolysis/mitochondrial dysfunction and downregulated adhesion pathways. Trajectory analysis shows diminished syncytial precursors, suggesting impaired fusion capacity. Immune profiling identifies depleted TREM2+ Hofbauer macrophages and expanded interferon-responsive NK cells. Cell-cell interaction mapping demonstrates enhanced IFNG-IFNGR1-STAT1 signaling between VCT_LDHA and immune cells, alongside weakened VCT_TP63-stromal crosstalk. This study defines a maladaptive triad of metabolic stress, inflammation, and structural disintegration in sFGR, contributing to sFGR pathogenesis.
Published in
Single-cell insights into trophoblast heterogeneity and adaptive dysfunction in selective fetal growth restriction
Bi Y, Yang J, Li X et al. · Communications biology 2026 · PMID 41845016 · doi:10.1038/s42003-026-09798-2
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Also filed as BioProject PRJNA1392643 and SRA study SRP657478. Searching any of these in the dataset finder brings you back here.

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