How Embryonic Stem Cells Can Become Any Cell

A new understanding of the mechanisms giving embryonic stem cells their plasticity could allow manipulation of es cells in the laboratory to be used for treating degenerative diseases

New research at the Hebrew University of Jerusalem sheds light on pluripotency—the ability of embryonic stem cells to renew themselves indefinitely and to differentiate into all types of mature cells.

Solving this problem - which is a major challenge in modern biology - could expedite the use of embryonic stem cells in cell therapy and regenerative medicine.

If scientists can replicate the mechanisms that make pluripotency possible, they could create 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.

In fact, these processes were found by researchers in the lab of Dr. Eran Meshorer, in the Department of Genetics at the Hebrew University's Alexander Silberman Institute of Life Sciences, combine molecular, microscopic and genomic approaches. Meshorer's team is focusing on epigenetic pathways—which cause biological changes without changing the DNA sequence—that are specific to embryonic stem cells.

The specific groundbreaking research was performed by Shai Melcer, a PhD student in the Meshorer lab.

The molecule which is the basis for epigenetic
mechanisms is chromatin.

Chromatin is made up of a cell's DNA
with the addition of structural and regulatory proteins.

In embryonic stem cells,
an "open" chromatin configuration
means chromatin is less condensed.

This allows the molecule to have the flexibility
- or "functional plasticity"-
to turn into any kind of cell.

A distinct pattern of chemical modifiers on the chromatin structural proteins (referred to as acetylation and methylation of histones) enables a looser chromatin configuration in embryonic stem cells. During the early stages of differentiation, this pattern changes to facilitate chromatin compaction.

But even more interestingly, the authors found
that a nuclear lamina protein -
lamin A - is a big part of the secret.

In all differentiated cell types,
lamin A binds compacted domains of chromatin,
anchoring those domains to the cell's nuclear wall.

Lamin A is absent from embryonic stem cells
and this may enable the unanchored,
now more dynamic chromatin,
with in the cell nucleus.

The authors believe that chromatin plasticity is critical to functional plasticity since chromatin is made up of DNA that includes all genes and codes for all proteins in any living cell. Understanding the mechanisms that regulate chromatin function will enable intelligent manipulations of embryonic stem cells in the future.

Dr. Meshorer: "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.

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."

The research was funded by grants from 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 research appears in the journal Nature Communications as Melcer et al., Histone modifications and lamin A regulate chromatin protein dynamics in early embryonic stem cell differentiation.

Original article: http://www.eurekalert.org/pub_releases/2012-07/thuo-rim071812.php