Epigenetic Changes Regulating Epithelial-Mesenchymal Plasticity in Human Trophoblast Differentiation

Area of Science:

• Reproductive Biology
• Epigenetics
• Cellular Differentiation

Background:

• Human placental extravillous trophoblast (EVT) differentiation is critical for normal pregnancy.
• Abnormal EVT invasion is linked to major obstetric pathologies like preeclampsia and fetal growth restriction.
• Understanding normal EVT differentiation is key to analyzing these pathologies.

Purpose of the Study:

• To characterize the differentiation process of human villous cytotrophoblast (CTB) to EVT.
• To identify epigenetic mechanisms regulating trophoblast differentiation and plasticity.
• To investigate the role of specific genes, like RUNX1, in trophoblast function.

Main Methods:

• Purified human CTB and EVT cells were used for gene expression analysis.
• DNA methylation profiling was performed to assess epigenetic changes.
• Functional assays were conducted to evaluate the role of RUNX1 in trophoblast cell migration and invasion.

Main Results:

• CTB-EVT differentiation involves a mechanism resembling epithelial-mesenchymal transition (EMT).
• Genome-wide hypomethylation occurs during CTB to EVT transition, with specific genes undergoing gains of methylation (GOM).
• RUNX1 was identified as a key transcription factor regulating trophoblast migratory and invasive capacities through GOM-differential gene expression (DE).

Conclusions:

• Epigenetically regulated genes underpin the epithelial-mesenchymal plasticity essential for human trophoblast differentiation.
• RUNX1 plays a functional role in regulating trophoblast cell migration and invasion.
• These findings offer insights into obstetric disorders associated with dysregulated trophoblast differentiation and invasion.