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Discovery Of Novel Gene Regulatory System May Advance Neural Stem Cell Treatments.

LA JOLLA, Calif., January 24, 2018 -- Scientists here have discovered a novel gene regulatory system that may advance stem cell therapies and gene-targeting treatments for neurological diseases.

Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) have described how an mRNA modification impacts the life of neural stem cells (NSCs).

"Being able to maintain viable stem cells in the brain could lead to regenerative therapies to treat injury and disease," said Jing Crystal Zhao.

The study reveals a previously unknown but essential function of an mRNA modification in regulating NSC self-renewal.

As NSCs are increasingly explored as a cell replacement therapy for neurological disorders, understanding the basic biology of NSCs--including how they self-renew--is essential to harnessing control of their in vivo functions in the brain.

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

The study focused on the self-renewal aspect of NSCs. Using knockout mice (KO) for the enzyme that catalyzes the m6A modification, the team found that m6A modification maintain NSC pool by promoting proliferation and preventing premature differentiation of NSCs.

They found that m6A modification regu-and package DNA. Their modifications play an important role in whether genes are turned "on" or "off."

Some histone modifications compact the DNA to hide a gene from the cell's protein-making machinery and consequently turn gene "off." They can also loosen up DNA for gene exposure to turn gene "on."

The findings are the first to illustrate crosstalk between mRNA and histone modifications, and may lead to new ways to target genes in the brain, Zhao said.

"Conceptually, we could use the modification, which is the methylation of adenosine residue, as a 'code' in mRNA to target histone modifications to turn gene on or off," Zhao said.

Drugs that alter histones have a long history of use in psychiatry and neurology, and increasingly in cancer But current drugs tha modify histones are often times non-specific; they work across the entire genome.

The study addressed the interaction between mRNA and histone modification in a genome-wide scale. In the future, the researchers 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, they hope to correct aberrant gene expression in brain disorders with precision.

Citation: 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

Abstract/Article: Contact: Jing Crystal Zhao,

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Title Annotation:Basic Research
Publication:Stem Cell Research News
Date:Jan 29, 2018
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