Teratogen screening using transcriptome profiling of differentiating human embryonic stem cells.
Teratogens are substances that may cause defects in normal embryonic development while not necessarily being toxic in adults. Identification of possible teratogenic compounds has been historically beset by the species-specific nature of the teratogen response. To examine teratogenic effects on early human development we performed non-biased expression profiling of differentiating human embryonic and induced pluripotent stem cells treated with several drugs--ethanol, lithium, retinoic acid (RA), caffeine and thalidomide, which is known to be highly species specific. Our results point to the potency of specific teratogens and their affected tissues and pathways. Specifically, we could show that ethanol caused dramatic increase in endodermal differentiation, RA caused misregulation of neural development and thalidomide affected both these processes. We thus propose this method as a valuable addition to currently available animal screening approaches.
Mayshar
Yoav
Y
Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem, Israel.
Yanuka
Ofra
O
Benvenisty
Nissim
N
D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D058732:Embryoid Bodies / Q000187:drug effects* / Q000473:pathology; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000473:pathology; D004707:Endoderm / Q000187:drug effects* / Q000473:pathology; D000431:Ethanol / Q000009:adverse effects; D020869:Gene Expression Profiling / Q000379:methods; D057166:High-Throughput Screening Assays; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects* / Q000473:pathology; D055495:Neurogenesis / Q000187:drug effects; D013723:Teratogens / Q000494:pharmacology*; D013792:Thalidomide / Q000009:adverse effects; D014212:Tretinoin / Q000009:adverse effects
D013723:Teratogens; D000431:Ethanol; D013792:Thalidomide; D014212:Tretinoin