Extracellular vesicles facilitate cellular communication

Extracellular vesicles (EVs) are tiny bubbles released by cells, acting as cargo vessels through which cells exchange signals and thus communicate. A paper recently published in the journal Cell Reports demonstrated that this form of cellular exchange also plays a key role in brain development.

“Our results highlight the central role of EVs in intercellular signaling during brain development, highlighting their potential as mediators of complex cellular interactions and as targets for future therapeutic strategies,” says lead researcher Dr. Silvia Cappello, research group leader at LMU Biomedical Center and member of the SyNergy Cluster of Excellence.

The team studied extracellular vesicles in a variety of model systems, including neural stem cells, neurons, astrocytes, brain organoids, and patterned spheroids, all derived from pluripotent stem cells. The researchers gained new insights into how the small transport bubbles influence brain development.

One of the key findings of the study is that extracellular vesicles facilitate specialized communication between different cell types. “We demonstrated that recipient cells absorb cargo from different donor cells, for which they have unique uptake patterns,” Cappello says. This highlights the specificity of extracellular vesicle-mediated communication.

The researchers also found that the protein composition of vesicles changes during brain development and varies across cell populations and brain regions. “This variability suggests a tightly regulated biogenesis of vesicles, which is essential for their cell-type-specific functions,” Cappello says.

Using high-resolution live imaging techniques, the team was also able to show that extracellular vesicles enter the nucleus of neural stem cells during cell division. “This discovery is particularly exciting because it indicates that extracellular vesicles influence crucial cellular processes not only in the cytoplasm, but also at the nuclear level.”

The study revealed that the transported cargo includes proteins, but also transcription factors, such as YAP1, which are directly transferred to recipient cells and induce rapid transcriptional changes. A particularly interesting example is the transcription factor YAP1, which is directly transported to the nucleus of recipient cells, where it induces transcriptional changes.

“This ability of extracellular vesicles to transport specific molecular signals to the cell nucleus opens new avenues for our understanding of complex cellular interactions in the brain,” Cappello says.

According to the authors, these results highlight the central role of EVs in brain development and could pave the way for new therapeutic approaches for the treatment of long-term neurological diseases.