iScience (Sep 2020)

Fatty Acid Synthesis Is Indispensable for Survival of Human Pluripotent Stem Cells

  • Sho Tanosaki,
  • Shugo Tohyama,
  • Jun Fujita,
  • Shota Someya,
  • Takako Hishiki,
  • Tomomi Matsuura,
  • Hiroki Nakanishi,
  • Takayo Ohto-Nakanishi,
  • Tomohiko Akiyama,
  • Yuika Morita,
  • Yoshikazu Kishino,
  • Marina Okada,
  • Hidenori Tani,
  • Yusuke Soma,
  • Kazuaki Nakajima,
  • Hideaki Kanazawa,
  • Masahiro Sugimoto,
  • Minoru S.H. Ko,
  • Makoto Suematsu,
  • Keiichi Fukuda

Journal volume & issue
Vol. 23, no. 9
p. 101535

Abstract

Read online

Summary: The role of lipid metabolism in human pluripotent stem cells (hPSCs) is poorly understood. We have used large-scale targeted proteomics to demonstrate that undifferentiated hPSCs express different fatty acid (FA) biosynthesis-related enzymes, including ATP citrate lyase and FA synthase (FASN), than those expressed in hPSC-derived cardiomyocytes (hPSC-CMs). Detailed lipid profiling revealed that inhibition of FASN resulted in significant reduction of sphingolipids and phosphatidylcholine (PC); moreover, we found that PC was the key metabolite for cell survival in hPSCs. Inhibition of FASN induced cell death in undifferentiated hPSCs via mitochondria-mediated apoptosis; however, it did not affect cell survival in hPSC-CMs, neurons, or hepatocytes as there was no significant reduction of PC. Furthermore, we did not observe tumor formation following transplantation of FASN inhibitor-treated cells. Our findings demonstrate the importance of de novo FA synthesis in the survival of undifferentiated hPSCs and suggest applications for FASN inhibition in regenerative medicine.

Keywords