title: A genomics-based framework for identifying biomarkers of human neurodevelopmental toxicity.
abstract: Human embryonic stem cell (hESC) neural differentiation models have tremendous potential for evaluating environmental compounds in terms of their ability to induce neurodevelopmental toxicity. Genomic based-approaches are being applied to identify changes underlying normal human development (in vitro and in vivo) and the effects of environmental exposures. Here, we investigated whether mechanisms that are shared between hESC neural differentiation model systems and human embryos are candidate biomarkers of developmental toxicities for neurogenesis. We conducted a meta-analysis of transcriptomic datasets with the goal of identifying differentially expressed genes that were common to the hESC-model and human embryos. The overlapping NeuroDevelopmental Biomarker (NDB) gene set contained 304 genes which were enriched for their roles in neurogenesis. These genes were investigated for their utility as candidate biomarkers in the context of toxicogenomic studies focused on the effects of retinoic acid, valproic acid, or carbamazepine in hESC models of neurodifferentiation. The results revealed genes, including 13 common targets of the 3 compounds, that were candidate biomarkers of neurotoxicity in hESC-based studies of environmental toxicants.
authors.affiliation: Center for Reproductive Sciences, University of California, San Francisco (UCSF), United States; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco (UCSF), United States; The Eli & Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco (UCSF), United States. Electronic address: Joshua.Robinson@ucsf.edu.
authors.forename: J F
authors.initials: JF
authors.lastname: Robinson
authors.affiliation: Center for Reproductive Sciences, University of California, San Francisco (UCSF), United States; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco (UCSF), United States; The Eli & Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco (UCSF), United States.
authors.forename: M J
authors.initials: MJ
authors.lastname: Gormley
authors.affiliation: Center for Reproductive Sciences, University of California, San Francisco (UCSF), United States; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco (UCSF), United States; The Eli & Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco (UCSF), United States; Division of Maternal Fetal Medicine, University of California, San Francisco (UCSF), United States; Department of Anatomy, University of California, San Francisco (UCSF), United States; Human Embryonic Stem Cell Program, University of California, San Francisco (UCSF), United States.
authors.forename: S J
authors.initials: SJ
authors.lastname: Fisher
mesh_terms: D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation; D053595:Embryonic Stem Cells; D018507:Gene Expression Regulation, Developmental; D023281:Genomics; D006801:Humans; D055495:Neurogenesis / Q000235:genetics*; D020258:Neurotoxicity Syndromes / Q000235:genetics; D051381:Rats; D015027:Zebrafish
chemical_list: D015415:Biomarkers
keywords: Environmental exposures; Genomics; Human development; Human embryonic stem cells; Meta-analyses; Neurodevelopment; Neuron; Neurotoxicity
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