A University of Tokyo research team has identified two distinct control mechanisms in the developmental transition of undifferentiated stem cells into healthy brain cells.
The discovery involves the epigenetic control mechanisms of how neural stem cells lose the potential to produce neurons. This knowledge of developing stem cells into healthy brain cells may inform future regenerative medicine treatments for neurodegenerative diseases and spinal cord injuries.
How stem cells develop
During embryo development, stem cells differentiate into the types of cells the adult will need. Neural stem cells begin by differentiating into neurons (nerve cells) and then into astrocytes, which are support cells in the brain. Neural stem cells lose their potential to produce neurons as the embryo matures.
Growing healthy brain cells
The researchers collected neural stem cells from the brains of mouse embryos that grew inside their mother until 11 days after conception. The researchers separated cells into two groups to grow outside the body for different periods of time. One group was grown until the early stage of neural development when neurons are formed. The other group was grown until the later stage of cells turning into astrocytes.
Professor Yukiko Gotoh at the University of Tokyo leads the team of scientists. Gotoh said: “It is a paradox for regenerative medicine that neural stem cells produce fewer cells as they differentiate into additional cell types. We would like to grow specific cell types and lots of them.”
Gotoh added: “Neural stem cells must keep track of their own calendar. Even while growing outside the body they differentiate normally into neurons and then into astrocytes.”
The researchers discovered that PRC1 represses genes related to neuronal function. It does this by adding a molecule called ubiquitin during early stages of brain development when neural stem cells produce neurons. Then, at the later stages of brain development when stem cells produce astrocytes, the ubiquitin-adding becomes unnecessary. At this late stage, the PRC1 instead becomes polymers on these genes.
PRC1 represses the genes related to neuronal function transiently in the early stage, and permanently in the late stage of brain development.
The potential applications of this research
Understanding how the brain develops stem cells has provided an insight into designing treatments for neurodegenerative conditions, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, or to treat neuron damage elsewhere in the body, including spinal cord injuries