title: Ethanol alters proliferation and differentiation of normal and chromosomally abnormal human embryonic stem cell-derived neurospheres.
abstract: Ethanol is a powerful substance and, when consumed during pregnancy, has significant psychoactive and developmental effects on the developing fetus. These abnormalities include growth retardation, neurological deficits, and behavioral and cognitive deficiencies, commonly referred to as fetal alcohol spectrum disorder. The effect of ethanol has been reported to affect cellular development on the embryonic level, however, not much is known about mutations contributing to the influence of ethanol. The purpose of our study was to determine if mutation contribute to changes in differentiation patterning, cell-cycle regulatory gene expression, and DNA methylation in human embryonic stem cells after ethanol exposure. We exposed human embryonic stem cells (with and without know DNA mutations) to a low concentration (20 mM) of ethanol and measured neurosphere proliferation and differentiation, glial protein levels, expression of various cell-cycle genes, and DNA methylation. Ethanol altered cell-cycle gene expression between the two cell lines; however, gene methylation was not affected in ether lines.
authors.affiliation: Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Malini
authors.initials: M
authors.lastname: Krishnamoorthy
authors.forename: Brian A
authors.initials: BA
authors.lastname: Gerwe
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Scharer
authors.forename: Vanita
authors.initials: V
authors.lastname: Sahasranaman
authors.forename: Carmen D
authors.initials: CD
authors.lastname: Eilertson
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Nash
authors.forename: Sümeyra Naz
authors.initials: SN
authors.lastname: Usta
authors.forename: Shasmine
authors.initials: S
authors.lastname: Kelly
authors.forename: Matthew
authors.initials: M
authors.lastname: Rose
authors.forename: Rene
authors.initials: R
authors.lastname: Peraza
authors.forename: Jagan
authors.initials: J
authors.lastname: Arumugham
authors.forename: Bethany
authors.initials: B
authors.lastname: Stewart
authors.forename: Steven L
authors.initials: SL
authors.lastname: Stice
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Nash
mesh_terms: D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002869:Chromosome Aberrations; D019175:DNA Methylation / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D000431:Ethanol / Q000633:toxicity*; D016195:G2 Phase / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects* / Q000473:pathology
chemical_list: D007211:Indoles; D012333:RNA, Messenger; D000431:Ethanol; C007293:DAPI; D001973:Bromodeoxyuridine