Transcriptomics analysis of early embryonic stem cell differentiation under osteoblast culture conditions: Applications for detection of developmental toxicity.

Autor: Chen X; Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, United States. Electronic address: xchen@cpsc.gov., Han T; Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, United States. Electronic address: Tao.Han@fda.hhs.gov., Fisher JE; Center for Drug Evaluation and Research, Food and Drug Administration, United States. Electronic address: Jedward.fisher@fda.hhs.gov., Harrouk W; Center for Drug Evaluation and Research, Food and Drug Administration, United States. Electronic address: Wafa.Harrouk@fda.hhs.gov., Tassinari MS; Center for Drug Evaluation and Research, Food and Drug Administration, United States. Electronic address: Melissa.Tassinari@fda.hhs.gov., Merry GE; Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, United States. Electronic address: Gwenn.Merry@fda.hhs.gov., Sloper D; Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, United States. Electronic address: Daniel.Sloper@fda.hhs.gov., Fuscoe JC; Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, United States. Electronic address: James.Fuscoe@fda.hhs.gov., Hansen DK; Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, United States. Electronic address: deborah_hansen@sbcglobal.net., Inselman AL; Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration, United States. Electronic address: Amy.Inselman@fda.hhs.gov.
Jazyk: angličtina
Zdroj: Reproductive toxicology (Elmsford, N.Y.) [Reprod Toxicol] 2017 Apr; Vol. 69, pp. 75-83. Date of Electronic Publication: 2017 Feb 08.
DOI: 10.1016/j.reprotox.2017.02.001
Abstrakt: 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.
(Published by Elsevier Inc.)
Databáze: MEDLINE
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