Discovery May Advance Neural Stem Cell Treatments For Brain Disorders
Source: Sanford-Burnham Prebys Medical Discovery Institute
Summary: A new study reveals a novel gene regulatory system that may advance stem cell therapies and gene-targeting treatments for neurological diseases.
Neural Stem Cells (NSCs) are progenitor cells present not only during embryonic development but also in the adult brain. NSCs undergo a self-renewal process to maintain their population, as well as differentiate to give rise to all neural cell types: neurons, astrocytes and oligodendrocytes. NSCs are increasingly explored as a cell replacement therapy for neurological disorders. Therefore the basic understanding, how they self-renew, is essential to harness the control of their in–vivo functions in the brain. A study done by the researchers from the Sanford-Burnham Prebys Medical Discovery Institute revealed a novel gene regulatory system that may advance stem cell therapies and gene-targeting treatments for neurological diseases. This research is among the first to describe how an mRNA modification impacts the life of NSCs. The study findings were published in the journal Nature Neuroscience.
Knockout mice (KO) for the enzyme that catalyzes the m6A (N6-Methyladenosine) modification was used and the research team found that m6A modification maintains NSC pool by promoting proliferation and preventing premature differentiation of NSCs. More specifically, the researchers found that m6A modification regulates this by regulating histone modifications. Histones are the proteins in cells that bind and package DNA and their modifications play an important role in whether genes are turned “on” or “off“. Conceptually, the modification (methylation of adenosine residues) can be used as a ‘code‘ in mRNA to target histone modifications to turn a gene on or off. These findings are the first to illustrate cross-talk between mRNA and histone modifications and may lead to new ways to target genes in the brain.
Asst. Prof. Jing Crystal Zhao said, “Our current study addressed the interaction between mRNA and histone modification in a genome-wide scale. In the future, we plan to study such interaction on a gene-by-gene basis. Ultimately, by modulating mRNA modification and its interacting histone modifications at a specific genomic region, we hope to correct aberrant gene expression in brain disorders with precision.”
More Information: Yang Wang et al, “N6-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications”, Nature Neuroscience (2018). DOI: 10.1038/s41593-017-0057-1