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

Uri Ben-David, Qing Fen Gan, Tamar Golan-Lev, Payal Arora, Ofra Yanuka, Yifat S. Oren, Alicia Leikin-Frenkel, Martin Graf, Ralph Garippa, Markus Boehringer, Gianni Gromo, Nissim Benvenisty*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

257 Scopus citations


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.

Original languageAmerican English
Pages (from-to)167-179
Number of pages13
JournalCell Stem Cell
Issue number2
StatePublished - 7 Feb 2013

Bibliographical note

Funding Information:
The authors would like to thank Hong Ma and Adva Maimon for their assistance with tissue culture; Dr. Eric Chiao, Dr. Josh Babiarz, Dr. Jenny Cohen, and Sei Kameoka for their assistance with assay development; Sean Walker for his assistance with the liquid handler; Dr. Ann Hoffman for her assistance with microscopy imaging; Dr. Rachel Eiges for her assistance with the in vitro embryonic development assay and for critically reading the manuscript; Dr. Sonia Steiner-Mordoch and Professor Oded Meyuhas for their assistance with the protein synthesis inhibition assay; Dr. Simona Ceccarelli for her assistance with the chemical analysis of compounds; Tamar Shiloach for her assistance with apoptosis assays; Dr. Eran Meshorer for the mouse ESCs and for critically reading the manuscript; Oded Kopper for the CSES2-SO2/3 cells; Professor Batsheva Kerem, Dr. Kyle Kolaja, Dr. Jacques Mizrahi, and Dr. David Mark for fruitful discussions and helpful suggestions. N.B. is the Herbert Cohn Chair in Cancer Research. U.B.-D. is a Clore Fellow. This work was supported by a grant from Hoffmann La Roche-Yissum collaboration. Q.F.G., M.G., M.B., and G.G. are employees of the company. R.G. and P.A. are former employees of the company.


Dive into the research topics of 'Selective elimination of human pluripotent stem cells by an oleate synthesis inhibitor discovered in a high-throughput screen'. Together they form a unique fingerprint.

Cite this