“New Ago2-associated microRNAs identified by deep sequencing in human embryonic stem cells.”
Ronald Hart,
Professor
Rutgers University
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Abstract: MicroRNAs are required for maintenance of pluripotency as well as differentiation, but since more microRNAs have been computationally predicted in genome than have been found, there are likely to be undiscovered microRNAs expressed early in stem cell differentiation. SOLiD ultra-deep sequences of small RNAs from human embryonic stem cells (hESC) and neural-restricted precursors were fit to a model of microRNA biogenesis to computationally predict new microRNA genes. These predicted genomic loci are associated with chromatin patterns of modified histones that are predictive of regulated gene expression. 146 of the predicted microRNAs were enriched in Ago2-containing complexes along with 609 known microRNAs, demonstrating association with a functional RISC complex. This Ago2 IP-selected subset was consistently expressed in four independent hESC lines and exhibited complex patterns of regulation over development similar to previously-known microRNAs, including pluripotency-specific expression in both hESC and iPS cells. Initial testing shows that cloned precursor hairpins are correctly processed into mature sequences and that microRNA function can be assayed in a high-throughput assay. Extending the classic definition of microRNAs, this large number of new microRNA genes, the majority of which are less conserved than their canonical counterparts, likely represent evolutionarily recent regulators of early differentiation.
Presenter Biography: Dr. Ronald P. Hart, member of the Rutgers Stem Cell Research Center and the W.M. Keck Center for Collaborative Neuroscience and a professor of Cell Biology & Neuroscience at Rutgers, The State University of New Jersey, is recognized as a leading expert in functional genomics technologies in the central nervous system and stem cells. Dr. Hart obtained a bachelor of science degree from The University of Connecticut and a doctorate from the University of Michigan Medical School. Following postdoctoral training at Rockefeller University, he joined the Rutgers (Newark) faculty in 1985.
In 2000, Dr. Hart was recruited to establish functional genomics technologies at the W. M. Keck Center for Collaborative Neuroscience where he also became a professor in the Department of Cell Biology and Neuroscience. Beginning with a pilot project funded by the Christopher Reeve Paralysis Foundation, Dr. Hart established the Neuroscience Gene Expression Laboratory (NGEL) within the W. M. Keck Center. Dr. Hart has trained over 75 national and international scientists in the use of microarrays and actively works in partnership with dozens of researchers throughout the world.
Dr. Hart’s specialty is molecular biology and the expression and processing of RNA in cells. Dr. Hart was one of the first to identify specific mechanisms linking inflammation in the nervous system to the activation of growth and differentiation factors. His laboratory cloned many of the first inflammatory cytokines from the rat nervous system and has made these available to researchers worldwide. In 2001, Dr. Hart’s group published the first comprehensive gene expression analysis of acute spinal cord injury. In 2005, Dr. Hart was awarded one of the first New Jersey Stem Cell Research Grants. He is the author of over 60 publications.
Online Presentation: http://lifescience.planetconnect.com/ppt/LSPrinceton/tuesday/RONALD_HART.ppt
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