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.
