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FAD influx enhances neuronal differentiation of human neural stem cells by facilitating nuclear localization of LSD1

Flavin adenine dinucleotide (FAD), synthesized from riboflavin, is redox cofactor in energy production and plays an important role in cell survival. More recently, riboflavin deficiency has been linked to developmental disorders, but its role in stem cell differentiation remains unclear. Here, we sh...

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Detalles Bibliográficos
Autores principales: Hirano, Kazumi, Namihira, Masakazu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715241/
https://www.ncbi.nlm.nih.gov/pubmed/29226080
http://dx.doi.org/10.1002/2211-5463.12331
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author Hirano, Kazumi
Namihira, Masakazu
author_facet Hirano, Kazumi
Namihira, Masakazu
author_sort Hirano, Kazumi
collection PubMed
description Flavin adenine dinucleotide (FAD), synthesized from riboflavin, is redox cofactor in energy production and plays an important role in cell survival. More recently, riboflavin deficiency has been linked to developmental disorders, but its role in stem cell differentiation remains unclear. Here, we show that FAD treatment, using DMSO as a solvent, enabled an increase in the amount of intracellular FAD and promoted neuronal differentiation of human neural stem cells (NSCs) derived not only from fetal brain, but also from induced pluripotent stem cells. Depression of FAD‐dependent histone demethylase, lysine‐specific demethylase‐1 (LSD1), prevented FAD‐induced neuronal differentiation. Furthermore, FAD influx facilitated nuclear localization of LSD1 and its enzymatic activity. Together, these findings led us to propose that FAD contributes to proper neuronal production from NSCs in the human fetal brain during development.
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spelling pubmed-57152412017-12-08 FAD influx enhances neuronal differentiation of human neural stem cells by facilitating nuclear localization of LSD1 Hirano, Kazumi Namihira, Masakazu FEBS Open Bio Research Articles Flavin adenine dinucleotide (FAD), synthesized from riboflavin, is redox cofactor in energy production and plays an important role in cell survival. More recently, riboflavin deficiency has been linked to developmental disorders, but its role in stem cell differentiation remains unclear. Here, we show that FAD treatment, using DMSO as a solvent, enabled an increase in the amount of intracellular FAD and promoted neuronal differentiation of human neural stem cells (NSCs) derived not only from fetal brain, but also from induced pluripotent stem cells. Depression of FAD‐dependent histone demethylase, lysine‐specific demethylase‐1 (LSD1), prevented FAD‐induced neuronal differentiation. Furthermore, FAD influx facilitated nuclear localization of LSD1 and its enzymatic activity. Together, these findings led us to propose that FAD contributes to proper neuronal production from NSCs in the human fetal brain during development. John Wiley and Sons Inc. 2017-10-17 /pmc/articles/PMC5715241/ /pubmed/29226080 http://dx.doi.org/10.1002/2211-5463.12331 Text en © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Hirano, Kazumi
Namihira, Masakazu
FAD influx enhances neuronal differentiation of human neural stem cells by facilitating nuclear localization of LSD1
title FAD influx enhances neuronal differentiation of human neural stem cells by facilitating nuclear localization of LSD1
title_full FAD influx enhances neuronal differentiation of human neural stem cells by facilitating nuclear localization of LSD1
title_fullStr FAD influx enhances neuronal differentiation of human neural stem cells by facilitating nuclear localization of LSD1
title_full_unstemmed FAD influx enhances neuronal differentiation of human neural stem cells by facilitating nuclear localization of LSD1
title_short FAD influx enhances neuronal differentiation of human neural stem cells by facilitating nuclear localization of LSD1
title_sort fad influx enhances neuronal differentiation of human neural stem cells by facilitating nuclear localization of lsd1
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715241/
https://www.ncbi.nlm.nih.gov/pubmed/29226080
http://dx.doi.org/10.1002/2211-5463.12331
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