A potent and selective small molecule inhibitor of sirtuin 1 promotes differentiation of pluripotent P19 cells into functional neurons

Beom Seok Kim, Chang Hee Lee, Gyeong Eon Chang, Eunji Cheong, Injae Shin

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Sirtuin 1 (SIRT1) is known to suppress differentiation of pluripotent/multipotent cells and neural progenitor cells into neurons by blocking activation of transcription factors critical for neurogenesis. EX-527 is a highly selective and potent inhibitor against SIRT1 and has been used as a chemical probe that modulates SIRT1-associated biological processes. However, the effect of EX-527 on neuronal differentiation in pluripotent cells has not been well elucidated. Here, we report an examination of EX-527 effects on neurogenesis of pluripotent P19 cells. The results showed that EX-527 greatly accelerated differentiation of P19 cells into neurons without generation of cardiac cells and astrocytes. Importantly, neurons derived from P19 cells treated with EX-527 generated voltage-dependent sodium currents and depolarization-induced action potentials. The findings indicate that the differentiated cells have electrophysiological properties. The present study suggests that the selective SIRT1 inhibitor could have the potential of being employed as a chemical inducer to generate functionally active neurons.

Original languageEnglish
Article number34324
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 2016 Sep 29

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Sirtuin 1
Neurons
Neurogenesis
Biological Phenomena
Astrocytes
Action Potentials
Cell Differentiation
Transcription Factors
Stem Cells
Sodium
6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide

All Science Journal Classification (ASJC) codes

  • General

Cite this

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abstract = "Sirtuin 1 (SIRT1) is known to suppress differentiation of pluripotent/multipotent cells and neural progenitor cells into neurons by blocking activation of transcription factors critical for neurogenesis. EX-527 is a highly selective and potent inhibitor against SIRT1 and has been used as a chemical probe that modulates SIRT1-associated biological processes. However, the effect of EX-527 on neuronal differentiation in pluripotent cells has not been well elucidated. Here, we report an examination of EX-527 effects on neurogenesis of pluripotent P19 cells. The results showed that EX-527 greatly accelerated differentiation of P19 cells into neurons without generation of cardiac cells and astrocytes. Importantly, neurons derived from P19 cells treated with EX-527 generated voltage-dependent sodium currents and depolarization-induced action potentials. The findings indicate that the differentiated cells have electrophysiological properties. The present study suggests that the selective SIRT1 inhibitor could have the potential of being employed as a chemical inducer to generate functionally active neurons.",
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A potent and selective small molecule inhibitor of sirtuin 1 promotes differentiation of pluripotent P19 cells into functional neurons. / Kim, Beom Seok; Lee, Chang Hee; Chang, Gyeong Eon; Cheong, Eunji; Shin, Injae.

In: Scientific Reports, Vol. 6, 34324, 29.09.2016.

Research output: Contribution to journalArticle

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AU - Kim, Beom Seok

AU - Lee, Chang Hee

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AU - Shin, Injae

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