24 December 2012

Embryonic stem cells found a "differentiation switch"

Breakthrough in understanding the biology of embryonic stem cells

LifeSciencesToday based on Trinity College Dublin: Breakthrough in the Understanding of Embryonic Stem CellsA significant breakthrough in understanding the biology of embryonic stem cells has been made by scientists from the Smurfit Institute of Genetics at Trinity College Dublin, Ireland.

The data obtained during this study is of considerable interest for tissue engineering and regenerative medicine. A group led by Dr. Adrian Bracken, funded by the Science Foundation Ireland, recently published the results of their study in the journal Nature Structural & Molecular Biology (Polycomb PHF19 binds H3K36me3 and recruits PRC2 and demethylase NO66 to embryonic stem cell genes during differentiation).

A new study describes the process of "turning off" genes "turned on" in embryonic stem cells (ESCs), which is crucial for the transformation of stem cells into various types of differentiated cells, such as neurons, blood cells or heart cells. This is especially relevant due to the potential of these cells in the regeneration of affected tissues and organs, as well as in the treatment of a number of diseases, including Parkinson's disease, diabetes and spinal cord injuries. The work of Irish scientists also examines the epigenetic aspects of the differentiation of ESCs.

Epigenetics explains why body cells that have exactly the same set of genes are so functionally different. For example, a neuron and a muscle cell look and behave very differently, but their DNA contains the same genes. The study of epigenetics has helped scientists understand that each cell type has its own unique pattern of "off" and "on" genes. The appearance of cells of different types is explained by these differences.

The study by Irish scientists focuses on the role of the protein PHF19, belonging to the "Polycomb" group, in mouse embryonic stem cells. Gerard Brien, a graduate student in Dr. Bracken's laboratory, the lead author of the article, showed that without PHF19, embryonic stem cells are unable to generate specialized cells – heart, lung or brain cells. He found that PHF19 plays a crucial role in the "switching" of ESC genes from the "on" state to the "off" state during their transformation into specialized cells. The PHF19 protein does this by reading the epigenetic marker H3K36me3, which is found only on the expressed genes. PHF19 then recruits additional Polycomb and other proteins that replace H3K36me3 with another chemical label, H3K27me3, present on the "off" genes.

Commenting on the results, Dr. Bracken stated: "This discovery concerning PHF19 is an important step forward in our understanding of how stem cells specialize. In addition to its relevance for regenerative medicine, it may also have an impact on future cancer treatments. We are also studying the EZH2 protein close to PHF19, also from the Polycomb group, which is mutated in lymphoma, a type of blood cancer. For the treatment of such patients, several new drugs have been developed, the target of which is EZH2. The new data we have obtained suggest that patients with lymphoma can also be treated with PHF19 inhibitors. This work, funded by the Science Foundation of Ireland, is already underway."

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