Researchers from the University of Washington School of Medicine in St. Louis have transformed skin cells from healthy adults directly into motor neurons without going through a stem cell state.
Motor neurons drive muscle contractions and their damage underlies devastating diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy, both of which ultimately lead to paralysis and early death.
Unlike commonly studied mouse motor neurons, human motor neurons growing in the lab would be a new tool since researchers can’t take samples of these neurons from living people but can easily take skin samples.
“In this study, we only used skin cells from healthy adults ranging in age from early 20s to late 60s,” said senior author Andrew S. Yoo, Ph.D., an assistant professor of developmental biology.
“Our research revealed how small RNA molecules can work with other cell signals called transcription factors to generate specific types of neurons, in this case motor neurons,” Yoo said.
“In the future, we would like to study skin cells from patients with disorders of motor neurons. Our conversion process should model late-onset aspects of the disease using neurons derived from patients with the condition,” he added.
They did this by exposing skin cells in a lab to certain molecular signals usually found at high levels in the human brain. They focused on two short snippets of RNA: microRNAs (mRNAs) called miR-9 and miR-124, which are involved in repurposing the genetic instructions of the cell.
These mRNAs, combined with certain transcription factors, successfully turned skin cells into spinal cord motor neurons within just 30 days.
The ability of scientists to convert human skin cells into other cell types, such as neurons, has the potential to enhance understanding of disease and lead to finding new ways to heal damaged tissues and organs, a field called regenerative medicine.
The technique could help researchers better understand diseases of motor neurons, such as amyotrophic lateral sclerosis. The study was published in the journal Cell Stem Cell.