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

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...

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Detalles Bibliográficos
Autores principales: Tanosaki, Sho, Tohyama, Shugo, Fujita, Jun, Someya, Shota, Hishiki, Takako, Matsuura, Tomomi, Nakanishi, Hiroki, Ohto-Nakanishi, Takayo, Akiyama, Tomohiko, Morita, Yuika, Kishino, Yoshikazu, Okada, Marina, Tani, Hidenori, Soma, Yusuke, Nakajima, Kazuaki, Kanazawa, Hideaki, Sugimoto, Masahiro, Ko, Minoru S.H., Suematsu, Makoto, Fukuda, Keiichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509212/
https://www.ncbi.nlm.nih.gov/pubmed/33083764
http://dx.doi.org/10.1016/j.isci.2020.101535
Descripción
Sumario: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.