title: FOXO4 is necessary for neural differentiation of human embryonic stem cells.
abstract: Proteostasis is critical for maintaining cell function and proteome stability may play an important role in human embryonic stem cell (hESC) immortality. Notably, hESC populations exhibit a high assembly of active proteasomes, a key node of the proteostasis network. FOXO4, an insulin/IGF-1 responsive transcription factor, regulates proteasome activity in hESCs. We find that loss of FOXO4 reduces the potential of hESCs to differentiate into neural lineages. Therefore, FOXO4 crosses evolutionary boundaries and links hESC function to invertebrate longevity modulation.
authors.affiliation: Howard Hughes Medical Institute, Glenn Center for Aging Research, Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: David
authors.initials: D
authors.lastname: Vilchez
authors.forename: Leah
authors.initials: L
authors.lastname: Boyer
authors.forename: Margaret
authors.initials: M
authors.lastname: Lutz
authors.forename: Carsten
authors.initials: C
authors.lastname: Merkwirth
authors.forename: Ianessa
authors.initials: I
authors.lastname: Morantte
authors.forename: Chris
authors.initials: C
authors.lastname: Tse
authors.forename: Brian
authors.initials: B
authors.lastname: Spencer
authors.forename: Lesley
authors.initials: L
authors.lastname: Page
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.forename: William Travis
authors.initials: WT
authors.lastname: Berggren
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
authors.forename: Andrew
authors.initials: A
authors.lastname: Dillin
mesh_terms: D018797:Cell Cycle Proteins; D016922:Cellular Senescence; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D006801:Humans; D007334:Insulin-Like Growth Factor I; D008136:Longevity; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D034622:RNA Interference; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; C108803:FOXO4 protein, human; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; D007334:Insulin-Like Growth Factor I; D046988:Proteasome Endopeptidase Complex
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