Researchers from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) have discovered a new mechanism for cell differentiation in mouse embryonic and skeletal muscle stem cells. The findings were recently published in Molecular Cell.

Stem cells are the "blank slate" of biology, having the ability to develop, or differentiate, into many different types of cells. They also have the ability to stay in an uncommitted state for very long periods of time. In order to examine the mechanisms of cell development, the researchers focused their attention on a protein known to be involved in differentiation processes — Ezh2. This protein is part of a larger complex, called the Polycomb group (PcG), which influences cell differentiation by repressing developmental regulators in stem cells. In other words, PcG prevents a stem cell from developing and keeps it in an uncommitted state indefinitely. For a stem cell to differentiate, the PcG influence needs to be removed.

To find out how this happens, researchers in the NIAMS Laboratory of Muscle Cells and Gene Regulation, led by Vittorio Sartorelli, M.D., along with colleagues at the Whitehead Institute for Biomedical Research and the Massachusetts Institute of Technology in Cambridge, Mass., looked at mouse skeletal muscle and embryonic stem cells during the short window of time when the cells just started to differentiate. They found high levels of microRNA 214 (miR-214) in these cells. MicroRNAs are small strands of ribonucleic acid that work with proteins to carefully modulate gene expression. The researchers also found that they were able to induce the differentiation process in uncommitted cells by increasing levels of miR-214. Their results showed that miR-214 blocks Ezh2, thereby leading to the production of molecules that favor cell differentiation.

These finding may, in time, have applications for the use of human embryonic stem cells in research. If scientists can direct the differentiation of stem cells into specialized cells of their choosing, the cells may be used to model disease conditions, and to test new therapeutic approaches to human disease.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at 301-495-4484 or 877-22-NIAMS (free call) or visit the NIAMS Web site at

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Reference: Juan AH, Kumar RM, Marx JG, Young RA, Sartorelli V. Mir-214-dependent regulation of the polycomb protein Ezh2 in skeletal muscle and embryonic stem cells. Molecular Cell. 2009 Oct 9;36:61-74.

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