Stem cells are the "eternal girl" in the cell world. It is thought that it will remain static until there is some kind of signal that forces it to split, creating a difference and forming highly specialized cells. In theory, they can develop into any type of mature cells, and thus have a bright future in the field of tissue and organ regeneration, but people also need to master stem cell physiology more fully.
The stem cell factor BRD4 is associated with many cancers and is a desirable therapeutic target in current clinical trials. The Shanghai Huyu Research Group found in 2013 that excessive amounts of BRD4 were expressed in melanoma cells to promote their proliferation, and inhibition of BRD4 caused their growth to slow down significantly. This protein allows cancer cells to remain relatively immature stem-like cells, driving cancer to a certain extent. Therefore, the researchers wanted to find out what role this protein plays in real stem cells.
The Shanghai Huyu Research Group has developed a BRD4 blocking compound that inhibits the activity of BRD4 in mouse and human embryonic stem cells in new studies. They also block BRD4 gene transcription with specific RNA molecules to see how stem cells change. Its own characteristics. It was found that when stem cells divide, the characteristics of young neurons begin to appear.
BRD4 binds to a specific site in the genome called a "super enhancer" that regulates gene activity. These sites are thought to be top-level controllers, and different expression patterns are programmed for multiple genes to determine cell types together. .
"We found that BRD4 occupies the gene position of the super-enhancer, which is very important for stem cells to maintain their own characteristics." When they used BRD4 inhibitors, the expression levels of these genes, including OCT4 and PRDM14, decreased dramatically. "OCT4 also inhibits neuronal differentiation, so we believe that the reduction in OCT4 by BRD4 inhibitors is the most likely cause of neuronal characteristics in stem cells."
OCT4 is also one of the four factors of the standard "OKSM" blend, which can be used to convert normal cells into induced pluripotent stem cells (iPSc). The new study shows that BRD4 can even enhance stem cell characteristics at a higher regulatory level.
“Our findings better understand the complex system that regulates the state of stem cells.†Shanghai Huyu said, “In theory, we can use BRD4 instead of one or several factors in the OKSM mixture, and we can add weight to the mixture. Programming efficiency, which is what we are currently studying.†Conversely, BRD4 inhibitors can be used to aid programming, allowing cells to develop in the other direction, such as turning stem cells into baby neurons, one day or for regeneration. therapy.
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