Francis Crick Institute researchers have identified key genes
necessary for the conversion of astrocytes (cells that are
essential for maintaining neurons in the brain) to fully functional
neurons. They also uncovered a molecular mechanism that blocks this
reprogramming when astrocytes age.
The work has implications for repairing damage after a brain
injury or stroke.
Dr Sebastien Gillotin, one of the lead authors in Francois
Guillemot's lab at the Crick said: "Biologists are now able to
change the fate of a cell by changing the pattern of active genes
compared to the original cell type. For example, a skin cell can be
reprogrammed into a stem cell or a neuron.
"This new technique has changed our understanding of cellular
differentiation, where a cell changes from one type to another, and
raised hope for new medical treatments."
The team reprogrammed mouse astrocytes into neurons by
expressing Neurog2, a gene known to promote the development of
neurons.
They identified and isolated the genes involved and used
microscopy techniques to analyse the reprogramming efficiency.
To study the molecular mechanism at work, they used a mouse line
that was engineered to suppress the expression of a gene called
REST that was found to be responsible for the reprogramming
blockage.
Dr Gillotin said: "The brain is essentially made of three major
cell types: neurons, astrocytes and oligodendrocytes. After a
stroke or a brain injury, astrocytes proliferate in the affected
area to replace lost neurons that cannot be regenerated.
"Manipulation of the identified molecular blockage could allow
the re-expression of neuronal genes necessary for creating neurons
out of astrocytes in damaged brains."
The paper, Transcriptional Mechanisms of Proneural Factors and REST in
Regulating Neuronal Reprogramming of Astrocytes, is published
in Cell Stem Cell.