title: New insight into LSD1 function in human cortical neurogenesis.
abstract: The cerebral cortex of primates has evolved massively and intricately in comparison to that of other species. Accumulating evidence indicates that this is caused by changes in cell biological features of neural stem cells (NSCs), which differentiate into neurons and glial cells during development. The fate of NSCs during rodent cortical development is stringently regulated by epigenetic factors, such as histone modification enzymes, but the role of these factors in human corticogenesis is largely unknown. We have recently discovered that a lysine-specific demethylase 1 (LSD1), which catalyzes the demethylation of methyl groups in the histone tail, plays a unique role in human fetal NSCs (hfNSCs). We show that, unlike the role previously reported in mice, LSD1 in hfNSCs is necessary for neuronal differentiation and controls the expression ofHEYL, one of the NOTCH target genes, by modulating the methylation level of histones on its promoter region. Interestingly, LSD1-regulation ofHeylexpression is not observed in mouse NSCs. Furthermore, we first demonstrated that HEYL is able to maintain the undifferentiated state of hfNSCs. Our findings provide a new insight indicating that LSD1 may be a key player in the development and characterization of the evolved cerebral cortex.
authors.affiliation: Molecular Neurophysiology Research Group, Biomedical Research Institute, The National Institute of Advanced Industrial Science and Technology (AIST) , Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Hirano
authors.affiliation: Molecular Neurophysiology Research Group, Biomedical Research Institute, The National Institute of Advanced Industrial Science and Technology (AIST) , Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Namihira
keywords: HEYL; LSD1; cerebral cortex; epigenetics; histone methylation; neural stem cell; neurogenesis; notch