Identification of small molecules from human embryonic stem cells using metabolomics.
Metabolomics enables the discovery of small molecules that may serve as candidate biomarkers of pharmacological efficacy or toxicity. Biochemical pathways of human development are likely active in human embryonic stem (hES) cells and derivatives, since they recapitulate organogenesis in vitro. We hypothesized that small molecules could be measured from undifferentiated hES cells and hES cell-derived neural precursors (hNPs) using metabolomics and that these compounds are altered in response to known disruptors of human development. Metabolite profiling was performed in hES cells and hNPs after exposure to valproate, an inducer of neurodevelopmental disorders. Kynurenine, an intermediate in tryptophan metabolism, and other small molecules in glutamate metabolism were significantly upregulated in response to valproate. Thus, for the first time, we have been able to measure and identify small molecules secreted from hES cells and cells derived from hES cells. The hES cell metabolome may thus serve as a source of candidate biomarkers to predict or measure pharmacological efficacy or toxic response.
Cezar
Gabriela G
GG
Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA. ggcezar@wisc.edu
Quam
Jessica A
JA
Smith
Alan M
AM
Rosa
Guilherme J M
GJ
Piekarczyk
Marian S
MS
Brown
James F
JF
Gage
Fred H
FH
Muotri
Alysson R
AR
D015415:Biomarkers / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D017931:DNA Primers; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005492:Folic Acid / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007737:Kynurenine / Q000378:metabolism; D008660:Metabolism; D011761:Pyrrolidonecarboxylic Acid / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014635:Valproic Acid / Q000494:pharmacology
D015415:Biomarkers; D017931:DNA Primers; D011994:Recombinant Proteins; D007737:Kynurenine; D018698:Glutamic Acid; D014635:Valproic Acid; D005492:Folic Acid; D011761:Pyrrolidonecarboxylic Acid