Frontier: Molecule 'convinces' stem cells to become neurons
News from the Frontier

by Elizabeth Norton Lasley

July, 2008

A synthetic small molecule has been shown to nudge stem cells toward becoming neurons—an important step in guiding these precursors to develop into any type of tissue.

Stem cells are hailed for their potential to treat brain disorders in which specific neurons die off or are injured. Many such conditions affect areas where stem cells exist but don’t readily develop into neurons, thwarting efforts to boost production of replacement cells.

Molecular biologist Jenny Hsieh and colleagues at the University of Texas Southwestern Medical Center at Dallas had been looking for synthetic molecules that would guide stem cells to become cardiac muscle cells. But when some stem cells developed into neurons, the researchers took a closer look at the molecules they were screening.

Hsieh and colleagues found in cultured cells derived from rodent brains that one, dubbed Isoxazole-9, increased the rate at which stem cells became neurons and kept them from dividing or becoming “support” cells called astrocytes. The findings were reported online June 17 in Nature Chemical Biology. Unpublished preliminary data show similar results with lines of human stem cells.

Isoxazole-9 appears to act directly on a stem cell’s DNA, activating genes called transcription factors, whose role is to turn on other genes. “The ultimate goal of stem cell research is to take a cell from a patient’s own body, take it back down to stem cell level, and coax it into the type of cell that’s needed,” says Hsieh. “While this one molecule by itself doesn’t make that possible, it does act on the DNA to help the cell ‘commit’ to becoming a neuron.”