کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2593316 1562159 2016 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A genomics-based framework for identifying biomarkers of human neurodevelopmental toxicity
ترجمه فارسی عنوان
یک چارچوب مبتنی بر ژنومیک برای شناسایی بیومارکرهای سمیت تولید مثل در انسان است
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی


• Identified differentially expressed (DE) genes in hESC neurogenesis (n = 5 studies, in vitro).
• Described regulation of in vitro DE genes during human embryo development.
• Shared patterns (in vitro vs. human embryos) were enriched for neurogenesis genes.
• Carried out a preliminary verification of the candidate biomarkers.
• Initial results showed utility as sensitive markers of neurodevelopmental toxicity.

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Reproductive Toxicology - Volume 60, April 2016, Pages 1–10
نویسندگان
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