It is the research goal of many stem cell biologists to reveal the detailed mechanism by which embryonic stem cells differentiate to form terminal tissue types. Researchers from the University of Pennsylvania School of Medicine recently discovered a method for predicting cell fate based on histones in progenitor cell research. The research results were published online in the internationally renowned journal "Science".
Leading this research is Dr. Kenneth S. Zaret, professor of cell and developmental biology and deputy director of the Institute of Regenerative Medicine at the University of Pennsylvania. In recent years, Kenneth has focused his research on the fields of gene regulation, chromatin structure, development and stem cell biology. He has made a series of breakthrough research achievements and published many research papers in Science and Cell. He is currently the editor of MCB Magazine, and has served on various scientific research advisory committees, biotechnology and pharmaceutical companies, and NIH. At the same time, he also serves as Chairman of the Scientific Advisory Board of the National Institutes of Medicine (NIGMS) and a member of the American Association for the Advancement of Science (AAAS).
Understanding the mechanism by which developmental embryos assign different functions to different cell types is a key issue in developmental biology and regenerative medicine research. Over the past few years, Zaret's laboratory has been working to reveal the cell signaling network in mouse embryos that determines the differentiation of specific cell types. Researchers have confirmed that a specific cell growth factor can bind to specific receptors on the cell surface, and initiate specific chemical signals to determine cell fate, promote cell differentiation along the liver cell pathway, and inhibit its differentiation into pancreatic cells.
In the new study, the Zaret team confirmed that histone acetyltransferase P300 and histone methyltransferase Ezh2 play an important regulatory role in determining the transformation of cells into the fate of the liver or pancreas. When the researchers responded to the inhibition of these two enzymes in mice, they successfully induced embryonic cells to produce fewer liver cells and more pancreatic cells.
"We were surprised to find that before the fate of the cell is determined, there is a difference in the epigenetic marks of histones in embryonic cells that differentiate toward the liver or pancreas. This shows that we may be affected by manipulation of these histones The fate of cells may also be better predicted by detecting these histones in the early stages of differentiation, "Zaret said.
"The mechanism by which cells are identified for their special fate has always been an important research hotspot in developmental biology," said Dr. Susan Haynes, director of the Department of Genetics and Developmental Biology at the National Institutes of Health. The early stages of this process and provide new methods for controlling the fate of stem cells in regenerative medicine treatment. "
"By gaining a deeper understanding of the mechanism of normal cell programming, we will eventually be able to achieve accurate reprogramming of other cells," Zaret emphasized.
The researchers hope to develop new technologies based on this discovery to promote the development of embryonic stem cells for the treatment and research of liver or pancreatic beta cells, so as to solve the current shortage of pancreatic and liver tissues and provide patients with type 1 diabetes and acute liver failure Organ transplantation required. They are currently trying to simulate embryonic development steps to promote the differentiation of embryonic stem cells into mature cells. In addition, they hope to apply these findings to assess the epigenetic status of mid-stage progenitor cells. In the next study, the researchers also plan to use the generated liver cells and pancreatic cells to study and screen out drugs that can repair defects or promote cell growth.
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