Selective elimination of human pluripotent stem cells by an oleate synthesis inhibitor discovered in a high-throughput screen

Cell Stem Cell. 2013 Feb 7;12(2):167-79. doi: 10.1016/j.stem.2012.11.015. Epub 2013 Jan 11.


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 pluripotent cell-specific inhibitors (PluriSIns), nine of which share a common structural moiety. The PluriSIns selectively eliminated hPSCs while sparing a large array of progenitor and differentiated cells. Cellular and molecular analyses demonstrated that the most selective compound, PluriSIn #1, induces ER stress, protein synthesis attenuation, and apoptosis in hPSCs. Close examination identified this molecule as an inhibitor of stearoyl-coA desaturase (SCD1), the key enzyme in oleic acid biosynthesis, revealing a unique role for lipid metabolism in hPSCs. PluriSIn #1 was also cytotoxic to mouse blastocysts, indicating that the dependence on oleate is inherent to the pluripotent state. Finally, application of PluriSIn #1 prevented teratoma formation from tumorigenic undifferentiated cells. These findings should increase the safety of hPSC-based treatments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blastocyst / cytology
  • Blastocyst / drug effects
  • Blastocyst / metabolism
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Mice
  • Oleic Acid / chemical synthesis*
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / drug effects*
  • Pluripotent Stem Cells / metabolism
  • Stearoyl-CoA Desaturase / antagonists & inhibitors*


  • Enzyme Inhibitors
  • Oleic Acid
  • Stearoyl-CoA Desaturase