A*STAR Institute and Mayo Clinic Identify Key Protein to Convert Skin Cells into Other Types of Cells

Published: Jul 12, 2018 By

Stem Cells

A*STAR’s Institute of Molecular & Cell Biology (IMCB) in Singapore, along with the Mayo Clinic, identified a key epigenetic protein called H3.3 that helps convert skin cells into other types of cells via cellular reprogramming. The results were published in the journal Nature Communications in April.

The two groups found it was possible to engineer cells in the laboratory using a variety of methods, including differentiation, reprogramming and transdifferentiation, which are all closely controlled by epigenetic regulators. H3.3 is a major epigenetic regulator that can behave as a master switch for gene expression, turning it on or off, reprogramming cell types in the process.

With this discovery, the research groups are re-engineering skin cells to induce pluripotent stem cells to be used in clinical trials to treat patients with retinal degeneration. IMCB states, “The skin cells can also be easily converted to blood stem cells with approximately three times greater efficiency. This holds great potential for treating conditions that require the transplantation of matching bone marrow, such as leukemia.”

“A deeper understanding of epigenetic regulation, such as the roles of histone H3.3 variants on cell fate transition during cellular reprogramming will open the door for regenerative medicine to new clinical applications,” said Hu Li, associate professor of Systems Pharmacology at Mayo Clinic and co-lead researcher for the study, in a statement. “It will illuminate researchers and physicians to design treatments in a completely new way to treat and manage chronic diseases such as diabetes, heart failure, and neurodegenerative diseases.”

Also, today, A*STAR’s Genome Institute of Singapore (GIS), IMCB and the Stanford University School of Medicine found ways of generating pure liver cells from human stem cells. This has the potential for better ways to treat liver failure. The group also successfully grafted the generated liver cells into mouse models, which improved the mice’s short-term survival rate.

“Embryonic stem cells have the potential to turn into thousands of cell-types in the human body,” said Ang Lay Teng, senior research fellow at GIS, in a statement. She went on to say, “The key is to understand how to turn them solely into liver cells. Generating these highly-pure liver cells from embryonic stem cells is an important step towards using these cells for cell transplantation. The process of generating highly-pure liver cells involves a series of steps. As the whole process of liver development is not fully clear, one major challenge we faced was how to precisely control the development of stem cells into liver cells.”

Currently, end-stage liver failure is only treatable with liver transplants. More than one million patients die every year across the world waiting for transplants. The development of pure liver cells has the potential to be used to sustain patients until a liver is available.

Ng Huck Hui, executive director of GIS, stated, “The ability to generate large quantities of stem-cell derived liver cells holds the potential to sustain patients with liver failure while they await a full liver transplant. This holds great promise for helping to improve patient survival rates and alleviate the burden of liver failure on societies.”

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