Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-5-1
pubmed:abstractText
The effects of lithium chloride (LiCl) on differentiation of mouse embryonic stem (ES) cells were investigated in order to evaluate the ES cell test (EST) used in a European Union validation study for screening of embryotoxic agents in vitro. We show that LiCl inhibited concentration-dependently the differentiation of ES cells into cardiac and myogenic cells. Whereas the inhibition of cardiac differentiation by high concentrations of LiCl was obvious at day 5 + 5, decreased skeletal muscle cell differentiation was observed only at day 5 + 8. Semi-quantitative RT-PCR analyses revealed significantly lower levels of mRNA encoding cardiac-specific alpha-myosin heavy chain and skeletal muscle-specific myoD. By morphological investigation, an influence of lithium on neuronal differentiation was not evident. However, mRNA levels of genes encoding synaptophysin and the 160 kDa neurofilament protein were increased by high LiCl concentrations, whereas mRNA levels of mash-1 and Engrailed-1 were decreased, suggesting a specific influence of lithium on neuronal differentiation. Furthermore, LiCl treatment resulted in a slight, but non-significant increase of beta-catenin levels in ES cell-derived embryoid bodies. Our results demonstrate that the ES cell test, EST may be suitable to detect inhibitory effects of test compounds especially on cardiac differentiation, whereas effects on neuronal cells would not be detected. Therefore, we propose that morphological analyses of cardiac differentiation alone are insufficient to detect embryotoxic effects. The assay of other cell lineages at different developmental stages, and expression analyses of tissue-specific genes should also be employed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0214-6282
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
421-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11330862-Animals, pubmed-meshheading:11330862-Cell Differentiation, pubmed-meshheading:11330862-Cytoskeletal Proteins, pubmed-meshheading:11330862-Fluorescent Antibody Technique, pubmed-meshheading:11330862-Gene Expression Regulation, Developmental, pubmed-meshheading:11330862-Genes, pubmed-meshheading:11330862-Immunoblotting, pubmed-meshheading:11330862-Lithium Chloride, pubmed-meshheading:11330862-Mice, pubmed-meshheading:11330862-Muscle, Skeletal, pubmed-meshheading:11330862-Myocardium, pubmed-meshheading:11330862-Neurons, pubmed-meshheading:11330862-Organ Specificity, pubmed-meshheading:11330862-RNA, Messenger, pubmed-meshheading:11330862-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11330862-Stem Cells, pubmed-meshheading:11330862-Toxicity Tests, pubmed-meshheading:11330862-Trans-Activators, pubmed-meshheading:11330862-beta Catenin
pubmed:year
2001
pubmed:articleTitle
Lithium influences differentiation and tissue-specific gene expression of mouse embryonic stem (ES) cells in vitro.
pubmed:affiliation
In Vitro Differentiation Group, IPK Gatersleben, Germany.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't, Validation Studies