How a brain cell can change its mind

Harvard stem cell biologists have turned one type of already differentiated neurons into another within the brain.

The discovery, which is detailed in Nature Cell Biology, holds promise for a range of neurodegenerative diseases.

“These findings tell you that maybe the brain is not as immutable as we always thought, because at least during an early window of time one can reprogram the identity of one neuronal class into another,” said Paola Arlotta, Associate Professor in Havard’s Department of Stem Cell and Regenerative Biology (SCRB) who led the research.

In the study, the researchers targeted callosal projection neurons, which connect the brain’s two hemispheres. Using a transcription factor called Fezf2, they were able to reprogram these neurons to become corticospinal motor neurons, which are one of the two types of neuron destroyed in Amyotrophic Lateral Sclerosis (ALS) or Motor Neuron Disease.

Arlotta’s findings are particularly significant because the work was performed in vivo, in the brain of young living mice, rather than in-vitro, in collections of cells in culture dishes.

However, as young mice were used in the study, it is not yet known if the neuronal programming will be successful in older laboratory animals and consequently humans.

“Neurodegenerative diseases typically affect a specific population of neurons, leaving many others untouched. For example, in ALS it is corticospinal motor neurons in the brain and motor neurons in this spinal cord, among the many neurons of the nervous system, that selectively die,” Arlotta explained. “What is one could take neurons that are spared in a given diseases and turn them directly into the neurons that die off?”

Reference: Direct lineage reprogramming of post-mitotic callosal neurons into corticofugal neurons in vivo