Impact of Extracellular Vesicles Derived from Human Placenta Cells on Neural Progenitor Cell Transcriptome Dynamics

The fetal brain relies on the placenta for essential developmental signals, forming what is known as the placenta-brain axis. We hypothesize that extracellular vesicles (EVs) released by trophoblast (TB) cells transport small RNAs and other molecules from the placenta to the brain, influencing its early development. In this study, we isolated EVs from human TB cells differentiated in vitro and from their parental induced pluripotent stem cells (iPSCs). Small RNA sequencing revealed that TB-derived EVs contain distinct miRNAs, including hsa-miR-149-3p and hsa-miR-302a-5p, as well as long non-coding RNAs (lncRNAs), which are enriched in neural tissue. These TB-derived EVs are efficiently internalized by human neural progenitor cells (NPCs), leading to the induction of transcripts associated with forebrain formation and neurogenesis. Our findings provide insights into the role of the placenta-brain axis and suggest that TB-derived EVs may be key players in fetal neurodevelopment, offering potential biomarkers and therapeutic targets for neurobehavioral disorders like autism spectrum disorders (ASD).