title: Transcriptomics analysis of early embryonic stem cell differentiation under osteoblast culture conditions: Applications for detection of developmental toxicity.
abstract: The mouse embryonic stem cell test (mEST) is a promising in vitro assay for predicting developmental toxicity. In the current study, early differentiation of D3 mouse embryonic stem cells (mESCs) under osteoblast culture conditions and embryotoxicity of cadmium sulfate were examined. D3 mESCs were exposed to cadmium sulfate for 24, 48 or 72h, and whole genome transcriptional profiles were determined. The results indicate a track of differentiation was identified as mESCs differentiate. Biological processes that were associated with differentiation related genes included embryonic development and, specifically, skeletal system development. Cadmium sulfate inhibited mESC differentiation at all three time points. Functional pathway analysis indicated biological pathways affected included those related to skeletal development, renal and reproductive function. In summary, our results suggest that transcriptional profiles are a sensitive indicator of early mESC differentiation. Transcriptomics may improve the predictivity of the mEST by suggesting possible modes of action for tested chemicals.
authors.affiliation: Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, United States. Electronic address: xchen@cpsc.gov.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, United States. Electronic address: Tao.Han@fda.hhs.gov.
authors.forename: Tao
authors.initials: T
authors.lastname: Han
authors.affiliation: Center for Drug Evaluation and Research, Food and Drug Administration, United States. Electronic address: Jedward.fisher@fda.hhs.gov.
authors.forename: J Edward
authors.initials: JE
authors.lastname: Fisher
authors.affiliation: Center for Drug Evaluation and Research, Food and Drug Administration, United States. Electronic address: Wafa.Harrouk@fda.hhs.gov.
authors.forename: Wafa
authors.initials: W
authors.lastname: Harrouk
authors.affiliation: Center for Drug Evaluation and Research, Food and Drug Administration, United States. Electronic address: Melissa.Tassinari@fda.hhs.gov.
authors.forename: Melissa S
authors.initials: MS
authors.lastname: Tassinari
authors.affiliation: Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, United States. Electronic address: Gwenn.Merry@fda.hhs.gov.
authors.forename: Gwenn E
authors.initials: GE
authors.lastname: Merry
authors.affiliation: Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, United States. Electronic address: Daniel.Sloper@fda.hhs.gov.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sloper
authors.affiliation: Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, United States. Electronic address: James.Fuscoe@fda.hhs.gov.
authors.forename: James C
authors.initials: JC
authors.lastname: Fuscoe
authors.affiliation: Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, United States. Electronic address: deborah_hansen@sbcglobal.net.
authors.forename: Deborah K
authors.initials: DK
authors.lastname: Hansen
authors.affiliation: Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, United States. Electronic address: Amy.Inselman@fda.hhs.gov.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Inselman
mesh_terms: D000818:Animals; D019187:Cadmium Compounds / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D013431:Sulfates / Q000633:toxicity*
chemical_list: D019187:Cadmium Compounds; D013431:Sulfates; C037123:cadmium sulfate
keywords: Embryonic stem cell test; Embryotoxicity; Osteoblast; Transcriptomics