title: The DNA glycosylases OGG1 and NEIL3 influence differentiation potential, proliferation, and senescence-associated signs in neural stem cells.
abstract: Embryonic neural stem cells (NSCs) exhibit self-renewal and multipotency as intrinsic characteristics that are key parameters for proper brain development. When cells are challenged by oxidative stress agents the resulting DNA lesions are repaired by DNA glycosylases through the base excision repair (BER) pathway as a means to maintain the fidelity of the genome, and thus, proper cellular characteristics. The functional roles for DNA glycosylases in NSCs have however remained largely unexplored. Here we demonstrate that RNA knockdown of the DNA glycosylases OGG1 and NEIL3 decreased NSC differentiation ability and resulted in decreased expression of both neuronal and astrocytic genes after mitogen withdrawal, as well as the stem cell marker Musashi-1. Furthermore, while cell survival remained unaffected, NEIL3 deficient cells displayed decreased cell proliferation rates along with an increase in HP1γ immunoreactivity, a sign of premature senescence. Our results suggest that DNA glycosylases play multiple roles in governing essential neural stem cell characteristics.
authors.affiliation: Linnaeus Center in Developmental Biology for Regenerative Medicine, Department of Neuroscience, Karolinska Institutet, SE 17177 Stockholm, Sweden.
authors.forename: Amilcar
authors.initials: A
authors.lastname: Reis
authors.forename: Ola
authors.initials: O
authors.lastname: Hermanson
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D045647:DNA Glycosylases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; C491296:Msi1 protein, rat; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C024829:8-hydroxyguanine; D006147:Guanine; D014635:Valproic Acid; D045647:DNA Glycosylases; C483741:OGG1 protein, rat