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E-GEOD-37040 - Expression data from human pluripotent stem cells and differentiated cells treated with pluripotent-specific inhibitors

Status
Released on 22 January 2013, last updated on 2 June 2014
Organism
Homo sapiens
Samples (7)
Array (1)
Protocols (13)
Description
The use of human pluripotent stem cells (hPSCs) in cell therapy is hindered by the tumorigenic risk from residual undifferentiated cells. Here we performed a high-throughput screen of over 52,000 small molecules, and identified 15 highly selective cytotoxic inhibitors of hPSCs (PluriSIns). Cellular and molecular analyses revealed that the most selective compound, PluriSIn #1, is a pluripotent-specific inhibitor of stearoyl-coA desaturase (SCD1), the key enzyme in the biosynthesis of monounsaturated fatty acids (MUFA). SCD1 inhibition in hPSCs induced ER stress, protein synthesis attenuation, and apoptosis of these cells, revealing that MUFA biosynthesis is crucial for their survival. PluriSIn #1 was also cytotoxic toward the ICM cells of mouse embryos, indicating that the dependence on SCD1 is inherent to the pluripotent state. Finally, application of PluriSIn #1 prevented teratoma formation from tumorigenic undifferentiated cells. Our novel method to eliminate undifferentiated cells from culture should thus increase the safety of hPSC-based treatments. Expression data from undifferentiated and differentiated human embryonic stem cells. Total RNA was isolated from undifferentiated human pluripotent stem cells grown on matrigel with mTeSR1 medium, or from early endodermal progenitor cells differentiated from human embryonic stem cells.
Experiment type
transcription profiling by array 
Contacts
Citation
Selective Elimination of Human Pluripotent Stem Cells by an Oleate Synthesis Inhibitor Discovered in a High-Throughput Screen. Ben-David U, Gan QF, Golan-Lev T, Arora P, Yanuka O, Oren YS, Leikin-Frenkel A, Graf M, Garippa R, Boehringer M, Gromo G, Benvenisty N. , PMID:23318055
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-37040.idf.txt
Sample and data relationshipE-GEOD-37040.sdrf.txt
Raw data (1)E-GEOD-37040.raw.1.zip
Processed data (1)E-GEOD-37040.processed.1.zip
Array designA-AFFY-37.adf.txt
Links