PTB turn Astrocyte into neuron

For decades, Fu and his team at University of California San Diego School of Medicine studied a protein called PTB, which is well known for binding RNA and influencing which genes are turned "on" or "off" in a cell. To study the role of a protein like PTB, scientists often manipulate cells to reduce the amount of that protein, and then watch to see what happens.

Several years ago, a postdoctoral researcher working in Fu's lab was taking that approach, using a technique called siRNA to silence the PTB gene in connective tissue cells known as fibroblasts. But it's a tedious process that needs to be performed over and over. He got tired of it and convinced Fu they should use a different technique to create a stable cell line that's permanently lacking PTB. At first, the postdoc complained about that too, because it made the cells grow so slowly.

But then he noticed something odd after a couple of weeks—there were very few fibroblasts left. Almost the whole dish was instead filled with neurons.

In this serendipitous way, the team discovered that inhibiting or deleting just a single gene, the gene that encodes PTB, transforms several types of mouse cells directly into neurons.

Just a single treatment to inhibit PTB in mice converted native astrocytes, star-shaped support cells of the brain, into neurons that produce the neurotransmitter dopamine.

There are several different ways to mimic Parkinson's disease in mice. In this case, the researchers applied a dopamine look-a-like molecule to poison neurons that produce dopamine. As a result, the mice lose dopamine-producing neurons and develop symptoms similar to Parkinson's disease, such as movement deficiencies.

The treatment works like this: The researchers developed a noninfectious virus that carries an antisense oligonucleotide sequence—an artificial piece of DNA designed to specifically bind the RNA coding for PTB, thus degrading it, preventing it from being translated into a functional protein and stimulating neuron development.

Antisense oligonucleotides, also known as designer DNA drugs, are a proven approach for neurodegenerative and neuromuscular diseases—study co-author, Don Cleveland, Ph.D., pioneered the technology, and it now forms the basis for a Food and Drug Administration (FDA)-approved therapy for spinal muscular atrophy and several other therapies currently in clinical trials. 

 

어쩌다가 이 사실을 발견했고, Nature에도 기고했다. 신기하다 !

 

reference

 Reversing a model of Parkinson's disease with in situ converted nigral neurons, Nature (2020). DOI: 10.1038/s41586-020-2388-4 , www.nature.com/articles/s41586-020-2388-4