title: Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells.
abstract: BACKGROUND
  Studies have provided important findings about the roles of Notch signaling in neural development. Unfortunately, however, most of these studies have investigated the neural stem cells (NSCs) of mice or other laboratory animals rather than humans, mainly owing to the difficulties associated with obtaining human brain samples. It prompted us to focus on neuroectodermal spheres (NESs) which are derived from human embryonic stem cell (hESC) and densely inhabited by NSCs. We here investigated the role of Notch signaling with the hESC-derived NESs.
  
  
  RESULTS
  From hESCs, we derived NESs, the in-vitro version of brain-derived neurospheres. NES formation was confirmed by increased levels of various NSC marker genes and the emergence of rosette structures in which neuroprogenitors are known to reside. We found that Notch signaling, which maintains stem cell characteristics of in-vivo-derived neuroprogenitors, is active in these hESC-derived NESs, similar to their in-vivo counterpart. Expression levels of Notch signaling molecules such as NICD, DLLs, JAG1, HES1 and HES5 were increased in the NESs. Inhibition of the Notch signaling by a gamma-secretase inhibitor reduced rosette structures, expression levels of NSC marker genes and proliferation potential in the NESs, and, if combined with withdrawal of growth factors, triggered differentiation toward neurons.
  
  
  CONCLUSIONS
  Our results indicate that the hESC-derived NESs, which share biochemical features with brain-derived neurospheres, maintain stem cell characteristics mainly through Notch signaling, which suggests that the hESC-derived NESs could be an in-vitro model for in-vivo neurogenesis.
authors.affiliation: Development and Differentiation Research Center, KRIBB, 111 Gwahangno, Yuseong-gu, Daejeon 305-806, South Korea. wsm1959@hanmail.net
authors.forename: Sun-Mi
authors.initials: SM
authors.lastname: Woo
authors.forename: Janghwan
authors.initials: J
authors.lastname: Kim
authors.forename: Hyo-Won
authors.initials: HW
authors.lastname: Han
authors.forename: Jung-Il
authors.initials: JI
authors.lastname: Chae
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Son
authors.forename: Sunwha
authors.initials: S
authors.lastname: Cho
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Chung
authors.forename: Yong-Mahn
authors.initials: YM
authors.lastname: Han
authors.forename: Yong-Kook
authors.initials: YK
authors.lastname: Kang
mesh_terms: D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D039902:Multipotent Stem Cells / Q000166:cytology; D054258:Neural Plate / Q000166:cytology; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D051881:Receptor, Notch1 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C497761:NOTCH1 protein, human; D051881:Receptor, Notch1
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