CiRA researchers have made a new discovery in cell communication, finding that embryonic stem cells synchronize their differentiation through a system called phenotypic synchrony of cells, or PSyC. Cells in the body need to cooperate to carry out their functions and achieve their goals. They do this by communicating with one another, and this communication is essential for tissue and organ formation. The discovery sheds light on the ways in which cells synchronize their activities to achieve coordinated function.
Designing Embryonic Stem Cells for the Study of PSyC
Embryonic stem cells represent the earliest types of cells during embryo growth and are commonly used to study the first steps of body part development. To discover PSyC, the research team designed a special type of embryonic stem cell with protein kinase A constitutively active. This accelerated the differentiation of the cells. The researchers expected that mixing these embryonic stem cells with regular ones would disrupt synchronicity and result in two groups with different differentiation rates. However, that was not what they observed.
PSyC in Embryonic Stem Cells
The researchers found that even though there was initially a difference in differentiation rate, the normal embryonic stem cells eventually caught up to their protein kinase A counterparts. This catching up is what the study calls PSyC. However, this effect was only observed when the cells were in close proximity, and when they were separated, the effect was lost. This suggested that the cells in close proximity were communicating by passing vesicles between each other to perform PSyC.
Extracellular Vesicles and MicroRNA-132
Cells usually enclose the content inside an extracellular vesicle to exchange chemicals and molecules between one another. The extracellular vesicle is then released from the cell and absorbed by another, and then it opens to release its package inside the second cell. The researchers found that among the many types of biomolecules passed by extracellular vesicles was microRNA-132. This exchange induced the embryonic stem cells to mesoderm cells by PSyC. To prove this point, the researchers delivered microRNA-132 inside nanoparticles to the cells, finding the same effect.
Implications of the Study
CiRA Professor Jun Yamashita, who led the study, said that while the function of extracellular vesicles in cell communication was not new, the discovery that extracellular vesicles synchronize cell activity was. The findings suggest that extracellular vesicles can be used to synchronize cells for cell fate and differentiation. The study sheds light on the ways in which cells communicate and coordinate their activities to achieve coordinated function, which may have implications for future research in medicine and regenerative medicine.
Journal Information: Tomohiro Minakawa et al, Extracellular vesicles synchronize cellular phenotypes of differentiating cells, Journal of Extracellular Vesicles (2021). DOI: 10.1002/jev2.12147