A new Cedars-Sinai study in collaboration with the University of California, Irvine (UCI) and the Answer ALS consortium has examined the expression of thousands of genes in stem cell generated motor neurons that are known to die in patients with amyotrophic lateral sclerosis, a fatal neurological disorder known as ALS or Lou Gehrig's disease.
The study, published in the peer-reviewed journal Neuron, revealed sex was one of the main drivers of different gene expression in motor neurons, regardless of whether they were from patients diagnosed with ALS.
To understand why ALS happens and identify distinct molecular signatures of ALS in men and women, the team used 341 stem cell lines from ALS patients, which were differentiated into motor neurons, along with 92 lines from a healthy control group.
Leslie Thompson, PhD, co-corresponding author of the study and Bren professor of Psychiatry and Human Behavior and Neurobiology and Behavior at UCI, and her team performed and analyzed RNA sequencing that can measure the expression of up to 32,000 genes in each sample. This gives the teams the ability to detect gene patterns that may be affected by the disease and to see if there were any signals that would separate ALS patients from healthy controls.
Instead of finding prominent differences related to ALS, the team found striking differences between males and females, regardless of whether they were diagnosed with ALS. The investigators also were surprised to find that the male ALS stem cells generated significantly more motor neurons than the control group, but this was not observed with stem cells from females.
