MicroRNAs in Human Stem Cell Differentiation and 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.