Identification of small molecules from human embryonic stem cells using metabolomics

Area of Science:

• Biochemistry
• Developmental Biology
• Pharmacology

Background:

• Metabolomics identifies small molecules for assessing drug efficacy and toxicity.
• Human embryonic stem cells (hES) and their derivatives mimic human development in vitro.
• These cells offer a model to study developmental disruptions.

Purpose of the Study:

• To measure small molecules from hES cells and neural precursors (hNPs) using metabolomics.
• To investigate alterations in these small molecules in response to developmental disruptors.
• To establish hES cell-derived metabolites as potential biomarkers.

Main Methods:

• Metabolite profiling of hES cells and hNPs.
• Exposure of cells to valproate, a known neurodevelopmental disruptor.
• Analysis of small molecules, including those in tryptophan and glutamate metabolism.

Main Results:

• Successfully measured and identified small molecules secreted by hES cells and hNPs.
• Valproate exposure significantly upregulated kynurenine and other glutamate metabolism intermediates.
• Demonstrated the feasibility of using hES cell metabolomics for biomarker discovery.

Conclusions:

• The metabolome of hES cells and their derivatives can be measured.
• Specific metabolites are altered by developmental disruptors like valproate.
• hES cell-derived small molecules show promise as biomarkers for drug response and toxicity.