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

Overview

Journal iScience

Publisher Cell Press

Date 2020 Oct 21

PMID 33083764

Citations 32

Authors

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

Affiliations

Soon will be listed here.

Abstract

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 FA synthesis in the survival of undifferentiated hPSCs and suggest applications for FASN inhibition in regenerative medicine.

Citing Articles

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