MicroRNAs in Human Stem Cell Differentiation and Mental Disorders
Many mental disorders are closely associated with problems that occur during brain development in early life. For instance, by 2 years of age, autistic children have larger brains than normal kids, likely due to, at least in part, excess production of neurons and support cells, the building blocks of the nervous system. In autistic brains, how neurons grow various thread-like processes also shows some abnormalities. The cause of autism is complex and likely involves many genetic factors. These developmental defects are also associated with mental disorders caused by single-gene mutations, such as Rett syndrome and fragile X syndrome, the most common form of inherited mental retardation, whose clinical features overlap with autism. However, what causes the developmental defects in brains of children with different mental disorders is largely unknown. In recent years, an exciting new regulatory pathway was discovered that may well contribute to the etiology of mental disorders. The major player in this novel pathway is a class of tiny molecules 21
California is the most populated state in the US and has a large number of patients suffering from various mental disorders. The proposed studies in this grant application will contribute to the mission of developing novel avenues through stem cell research for the diagnosis, prevention and treatment of mental disorders
Human stem cells, both embryonic and induced pluripotent stem cells, offer exciting opportunities for cell-based therapies in injured or diseased human brains or spinal cords. The clinical efficacy of grafted progenitor cells critically depends on their ability to migrate to the appropriate sites in the adult central nervous system without unwanted proliferation and tumor formation. However, little is known about the cellular behavior of human neural progenitor cells derived from human stem cells or how their proliferation and migration are coordinated. During this reporting period, we continued to study human neural progenitor cells derived from human stem cells, a cell culture system established during the prior reporting period. We focused on microRNAs, a class of small, noncoding RNAs of ~21–23 nucleotides that regulate gene expression at the posttranscriptional level. These small RNAs mostly destabilize target mRNAs or suppress their translation by binding to complementary sequences in the 3' untranslated regions (3'UTRs). Our results obtained during this reporting period indicate that some microRNAs have very interesting functions in human neural progenitors, both in in vitro cell culture system and when transplanted into mouse brains. These new findings may have important implications for stem cell based therapies for neurodegenerative diseases or brain/spinal cord injuries.