|Photo by: Courtesy Hebrew University|
Breakthrough may help treat degenerative disease
By JUDY SIEGEL-ITZKOVICH
Hebrew U. researchers identify mechanism to transform embryonic stem cell into any human cell.
The most amazing property of embryonic stem cells is their capability of
renewing themselves an infinite number of times and differentiating into every
type of mature cell in the body – meaning they have the potential of serving as
the “factory” for producing healthy tissues to replace sick ones. But until now,
scientists did not know the secret behind this pluripotency, which if revealed
could eventually lead to their use to implant healthy new cells into humans
suffering from degenerative diseases – from Parkinson’s and Alzheimer’s disease
Doctoral student Shai Melcer and colleagues in the lab of
Hebrew University geneticist Dr. Eran Meshorer have just published their
research in the prestigious journal Nature Communications, reporting how they
identified the processes that turn human embryonic stem cells into any type of
The article titled “Histone modifications and lamin A regulate
chromatin protein dynamics in early embryonic stem cell differentiation”
discusses how the team combined molecular, microscopic and genomic approaches
and focused on epigenetic pathways, which cause biological changes without a
corresponding change in the DNA sequence and are specific to embryonic stem
The molecular basis for epigenetic mechanisms is chromatin, the
combination of DNA and proteins that make up the contents of the nucleus of a
Chromatin’s main functions are to package DNA into a smaller volume
to fit in the cell, strengthen the DNA to allow cell division and prevent harm
to the DNA, and control gene expression and DNA replication. The primary protein
components of chromatin are histones that compact the DNA.
In what is
described by Hebrew University as “groundbreaking research,” Melcer studied the
mechanisms that support an “open” chromatin conformation in embryonic stem
cells. The team found that chromatin is less condensed in embryonic stem cells,
allowing them the flexibility or “functional plasticity” to turn into any kind
A distinct pattern of chemical modifications of chromatin
structural proteins (referred to as the 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
They also found that a nuclear lamina protein called lamin A
is part of the secret.
In all differentiated cell types, lamin A binds
compacted domains of chromatin and anchors them to the cell’s nuclear envelope.
Lamin A is absent from embryonic stem cells and this may enable the freer, more
dynamic chromatin state in the cell nucleus. The authors believe that chromatin
plasticity is tantamount 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 in the future
enable intelligent manipulations of embryonic stem cells.
“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,” concluded Meshorer.