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Hebrew U team seeks the secret of embryonic stem cell ‘plasticity’

Researchers are trying to figure out how to use that flexibility in regenerative cell therapy

PhD student Shai Melcer (left) with Dr. Eran Meshorer at the Alexander Silberman Institute of Life Sciences, Hebrew University (Photo credit: Eran Meshorer)
PhD student Shai Melcer (left) with Dr. Eran Meshorer at the Alexander Silberman Institute of Life Sciences, Hebrew University (Photo credit: Eran Meshorer)

Researchers from Hebrew University have identified some of the mechanisms that give embryonic stem cells their special abilities and are working to apply them to degenerative diseases like Alzheimer’s, Parkinson’s, and diabetes, among others.

Embryonic stem cells can renew themselves indefinitely and can differentiate into various types of mature cells in any of the three germ layers: endoderm (interior stomach lining, gastrointestinal tract, the lungs), mesoderm (muscle, bone, blood, urogenital), or ectoderm (epidermal tissues and nervous system).

A team working in the lab of Dr. Eran Meshorer at Hebrew University’s Department of Genetics has been exploring epigenetic pathways — which cause biological changes without a corresponding change in the DNA sequence — that are specific to embryonic stem cells. They are part of a larger team that is taking a multi-pronged approach to research on degenerative disease, combining molecular, microscopic and genomic approaches.

The molecular basis for epigenetic mechanisms is chromatin, which comprises a cell’s DNA and structural and regulatory proteins. In groundbreaking research performed by Shai Melcer, a PhD student in the Meshorer lab, the mechanisms which support an “open” chromatin conformation in embryonic stem cells were examined. The researchers found that chromatin is less condensed in embryonic stem cells, allowing them the flexibility or “functional plasticity” to turn into any kind of cell.

They believe that if they can understand how this plasticity works, they will be able to manipulate embryonic stem cells in the future – and perhaps use them to replace cells that die off in degenerative diseases.

“If we can apply this new understanding about the mechanisms that give embryonic stem cells their plasticity, then we can increase or decrease the dynamics of the proteins that bind DNA and thereby increase or decrease the cells’ differentiation potential,” said Dr. Meshorer.

“This could expedite the use of embryonic stem cells in cell therapy and regenerative medicine, by enabling the creation of cells in the laboratory which could be implanted in humans to cure diseases characterized by cell death, such as Alzheimer’s, Parkinson’s, diabetes and other degenerative diseases.”

Research is ongoing, and is being funded by, among others, the European Union (ERC, Marie Curie), Israel Science Foundation, Ministry of Science, Ministry of Health, The National Institute for Psychobiology, Israel Cancer Research Foundation (ICRF), Abisch-Frenkel Foundation and Human Frontiers Science Program (HFSP), the Hebrew University said.

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