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Vitamin C induces a pluripotent state in mouse embryonic stem cells by modulating microRNA expression
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Zeitschriftentitel: | The FEBS Journal |
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Personen und Körperschaften: | , , , , , , , , , |
In: | The FEBS Journal, 282, 2015, 4, S. 685-699 |
Format: | E-Article |
Sprache: | Englisch |
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author_facet |
Gao, Yuan Han, Zhuo Li, Qian Wu, Yongyan Shi, Xiaoyan Ai, Zhiying Du, Juan Li, Wenzhong Guo, Zekun Zhang, Yong Gao, Yuan Han, Zhuo Li, Qian Wu, Yongyan Shi, Xiaoyan Ai, Zhiying Du, Juan Li, Wenzhong Guo, Zekun Zhang, Yong |
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author |
Gao, Yuan Han, Zhuo Li, Qian Wu, Yongyan Shi, Xiaoyan Ai, Zhiying Du, Juan Li, Wenzhong Guo, Zekun Zhang, Yong |
spellingShingle |
Gao, Yuan Han, Zhuo Li, Qian Wu, Yongyan Shi, Xiaoyan Ai, Zhiying Du, Juan Li, Wenzhong Guo, Zekun Zhang, Yong The FEBS Journal Vitamin C induces a pluripotent state in mouse embryonic stem cells by modulating microRNA expression Cell Biology Molecular Biology Biochemistry |
author_sort |
gao, yuan |
spelling |
Gao, Yuan Han, Zhuo Li, Qian Wu, Yongyan Shi, Xiaoyan Ai, Zhiying Du, Juan Li, Wenzhong Guo, Zekun Zhang, Yong 1742-464X 1742-4658 Wiley Cell Biology Molecular Biology Biochemistry http://dx.doi.org/10.1111/febs.13173 <jats:p>Micro<jats:styled-content style="fixed-case">RNA</jats:styled-content>s (mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s), a group of noncoding <jats:styled-content style="fixed-case">RNA</jats:styled-content>s, function as post‐transcriptional gene regulators and control the establishment, self‐renewal and differentiation of stem cells. Vitamin C has been recognized as a reprogramming enhancer because of its ability to induce a blastocyst‐like state in embryonic stem cells (<jats:styled-content style="fixed-case">ESC</jats:styled-content>s). However, knowledge on the regulation of mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s by vitamin C in <jats:styled-content style="fixed-case">ESC</jats:styled-content>s is limited. In this study, we found that vitamin C induced mi<jats:styled-content style="fixed-case">RNA</jats:styled-content> expression, particularly of <jats:styled-content style="fixed-case">ESC</jats:styled-content>‐specific mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s. Moreover, vitamin C maintained the mi<jats:styled-content style="fixed-case">RNA</jats:styled-content> expression of the <jats:italic>Dlk1</jats:italic>–<jats:italic>Dio3</jats:italic> imprinting region. The mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s in this region contain identical seed sequences, which target a class of genes, including <jats:italic>Kdm6b</jats:italic>,<jats:italic> Klf13</jats:italic>, and <jats:italic>Sox6</jats:italic>, and are mainly related to cell differentiation and development. These genes were significantly downregulated by vitamin C. Notably, miR‐143 promoted self‐renewal of mouse <jats:styled-content style="fixed-case">ESC</jats:styled-content>s and suppressed expression of the <jats:italic>de novo</jats:italic> methyltransferase gene <jats:italic>Dnmt3a</jats:italic>. Knockdown of miR‐143 by use of its inhibitor counteracted the vitamin C‐induced reduction in <jats:italic>Dnmt3a</jats:italic> expression, showing that vitamin C repressed <jats:italic>Dnmt3a</jats:italic> expression via miR‐143. Vitamin C also promoted <jats:styled-content style="fixed-case">DNA</jats:styled-content> demethylation, including of pluripotency gene promoters (<jats:italic>Tbx3</jats:italic>,<jats:italic> Tcl1</jats:italic>, and <jats:italic>Esrrb</jats:italic>) and <jats:styled-content style="fixed-case">ESC</jats:styled-content>‐specific mi<jats:styled-content style="fixed-case">RNA</jats:styled-content> promoters (miR‐290–295 and miR‐17–92 clusters), and <jats:styled-content style="fixed-case">DNA</jats:styled-content> hydroxymethylation, including of the intergenic differentially methylated region of the <jats:italic>Dlk1</jats:italic>–<jats:italic>Dio3</jats:italic> region. These results strongly suggested that vitamin C promoted widespread <jats:styled-content style="fixed-case">DNA</jats:styled-content> demethylation in gene promoters by modulating epigenetic modifiers, including <jats:italic>Dnmt3a</jats:italic>, which activated pluripotency genes and <jats:styled-content style="fixed-case">ESC</jats:styled-content>‐specific mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s. Then, differentiation and development genes were repressed by <jats:styled-content style="fixed-case">ESC</jats:styled-content>‐enriched mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s, which maintained the stem cell state.</jats:p> Vitamin C induces a pluripotent state in mouse embryonic stem cells by modulating micro<scp>RNA</scp> expression The FEBS Journal |
doi_str_mv |
10.1111/febs.13173 |
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Biologie Chemie und Pharmazie |
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Wiley, 2015 |
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Wiley, 2015 |
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2015 |
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Wiley |
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ai |
record_format |
ai |
series |
The FEBS Journal |
source_id |
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title |
Vitamin C induces a pluripotent state in mouse embryonic stem cells by modulating microRNA expression |
title_unstemmed |
Vitamin C induces a pluripotent state in mouse embryonic stem cells by modulating microRNA expression |
title_full |
Vitamin C induces a pluripotent state in mouse embryonic stem cells by modulating microRNA expression |
title_fullStr |
Vitamin C induces a pluripotent state in mouse embryonic stem cells by modulating microRNA expression |
title_full_unstemmed |
Vitamin C induces a pluripotent state in mouse embryonic stem cells by modulating microRNA expression |
title_short |
Vitamin C induces a pluripotent state in mouse embryonic stem cells by modulating microRNA expression |
title_sort |
vitamin c induces a pluripotent state in mouse embryonic stem cells by modulating micro<scp>rna</scp> expression |
topic |
Cell Biology Molecular Biology Biochemistry |
url |
http://dx.doi.org/10.1111/febs.13173 |
publishDate |
2015 |
physical |
685-699 |
description |
<jats:p>Micro<jats:styled-content style="fixed-case">RNA</jats:styled-content>s (mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s), a group of noncoding <jats:styled-content style="fixed-case">RNA</jats:styled-content>s, function as post‐transcriptional gene regulators and control the establishment, self‐renewal and differentiation of stem cells. Vitamin C has been recognized as a reprogramming enhancer because of its ability to induce a blastocyst‐like state in embryonic stem cells (<jats:styled-content style="fixed-case">ESC</jats:styled-content>s). However, knowledge on the regulation of mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s by vitamin C in <jats:styled-content style="fixed-case">ESC</jats:styled-content>s is limited. In this study, we found that vitamin C induced mi<jats:styled-content style="fixed-case">RNA</jats:styled-content> expression, particularly of <jats:styled-content style="fixed-case">ESC</jats:styled-content>‐specific mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s. Moreover, vitamin C maintained the mi<jats:styled-content style="fixed-case">RNA</jats:styled-content> expression of the <jats:italic>Dlk1</jats:italic>–<jats:italic>Dio3</jats:italic> imprinting region. The mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s in this region contain identical seed sequences, which target a class of genes, including <jats:italic>Kdm6b</jats:italic>,<jats:italic> Klf13</jats:italic>, and <jats:italic>Sox6</jats:italic>, and are mainly related to cell differentiation and development. These genes were significantly downregulated by vitamin C. Notably, miR‐143 promoted self‐renewal of mouse <jats:styled-content style="fixed-case">ESC</jats:styled-content>s and suppressed expression of the <jats:italic>de novo</jats:italic> methyltransferase gene <jats:italic>Dnmt3a</jats:italic>. Knockdown of miR‐143 by use of its inhibitor counteracted the vitamin C‐induced reduction in <jats:italic>Dnmt3a</jats:italic> expression, showing that vitamin C repressed <jats:italic>Dnmt3a</jats:italic> expression via miR‐143. Vitamin C also promoted <jats:styled-content style="fixed-case">DNA</jats:styled-content> demethylation, including of pluripotency gene promoters (<jats:italic>Tbx3</jats:italic>,<jats:italic> Tcl1</jats:italic>, and <jats:italic>Esrrb</jats:italic>) and <jats:styled-content style="fixed-case">ESC</jats:styled-content>‐specific mi<jats:styled-content style="fixed-case">RNA</jats:styled-content> promoters (miR‐290–295 and miR‐17–92 clusters), and <jats:styled-content style="fixed-case">DNA</jats:styled-content> hydroxymethylation, including of the intergenic differentially methylated region of the <jats:italic>Dlk1</jats:italic>–<jats:italic>Dio3</jats:italic> region. These results strongly suggested that vitamin C promoted widespread <jats:styled-content style="fixed-case">DNA</jats:styled-content> demethylation in gene promoters by modulating epigenetic modifiers, including <jats:italic>Dnmt3a</jats:italic>, which activated pluripotency genes and <jats:styled-content style="fixed-case">ESC</jats:styled-content>‐specific mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s. Then, differentiation and development genes were repressed by <jats:styled-content style="fixed-case">ESC</jats:styled-content>‐enriched mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s, which maintained the stem cell state.</jats:p> |
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author | Gao, Yuan, Han, Zhuo, Li, Qian, Wu, Yongyan, Shi, Xiaoyan, Ai, Zhiying, Du, Juan, Li, Wenzhong, Guo, Zekun, Zhang, Yong |
author_facet | Gao, Yuan, Han, Zhuo, Li, Qian, Wu, Yongyan, Shi, Xiaoyan, Ai, Zhiying, Du, Juan, Li, Wenzhong, Guo, Zekun, Zhang, Yong, Gao, Yuan, Han, Zhuo, Li, Qian, Wu, Yongyan, Shi, Xiaoyan, Ai, Zhiying, Du, Juan, Li, Wenzhong, Guo, Zekun, Zhang, Yong |
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container_title | The FEBS Journal |
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description | <jats:p>Micro<jats:styled-content style="fixed-case">RNA</jats:styled-content>s (mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s), a group of noncoding <jats:styled-content style="fixed-case">RNA</jats:styled-content>s, function as post‐transcriptional gene regulators and control the establishment, self‐renewal and differentiation of stem cells. Vitamin C has been recognized as a reprogramming enhancer because of its ability to induce a blastocyst‐like state in embryonic stem cells (<jats:styled-content style="fixed-case">ESC</jats:styled-content>s). However, knowledge on the regulation of mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s by vitamin C in <jats:styled-content style="fixed-case">ESC</jats:styled-content>s is limited. In this study, we found that vitamin C induced mi<jats:styled-content style="fixed-case">RNA</jats:styled-content> expression, particularly of <jats:styled-content style="fixed-case">ESC</jats:styled-content>‐specific mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s. Moreover, vitamin C maintained the mi<jats:styled-content style="fixed-case">RNA</jats:styled-content> expression of the <jats:italic>Dlk1</jats:italic>–<jats:italic>Dio3</jats:italic> imprinting region. The mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s in this region contain identical seed sequences, which target a class of genes, including <jats:italic>Kdm6b</jats:italic>,<jats:italic> Klf13</jats:italic>, and <jats:italic>Sox6</jats:italic>, and are mainly related to cell differentiation and development. These genes were significantly downregulated by vitamin C. Notably, miR‐143 promoted self‐renewal of mouse <jats:styled-content style="fixed-case">ESC</jats:styled-content>s and suppressed expression of the <jats:italic>de novo</jats:italic> methyltransferase gene <jats:italic>Dnmt3a</jats:italic>. Knockdown of miR‐143 by use of its inhibitor counteracted the vitamin C‐induced reduction in <jats:italic>Dnmt3a</jats:italic> expression, showing that vitamin C repressed <jats:italic>Dnmt3a</jats:italic> expression via miR‐143. Vitamin C also promoted <jats:styled-content style="fixed-case">DNA</jats:styled-content> demethylation, including of pluripotency gene promoters (<jats:italic>Tbx3</jats:italic>,<jats:italic> Tcl1</jats:italic>, and <jats:italic>Esrrb</jats:italic>) and <jats:styled-content style="fixed-case">ESC</jats:styled-content>‐specific mi<jats:styled-content style="fixed-case">RNA</jats:styled-content> promoters (miR‐290–295 and miR‐17–92 clusters), and <jats:styled-content style="fixed-case">DNA</jats:styled-content> hydroxymethylation, including of the intergenic differentially methylated region of the <jats:italic>Dlk1</jats:italic>–<jats:italic>Dio3</jats:italic> region. These results strongly suggested that vitamin C promoted widespread <jats:styled-content style="fixed-case">DNA</jats:styled-content> demethylation in gene promoters by modulating epigenetic modifiers, including <jats:italic>Dnmt3a</jats:italic>, which activated pluripotency genes and <jats:styled-content style="fixed-case">ESC</jats:styled-content>‐specific mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s. Then, differentiation and development genes were repressed by <jats:styled-content style="fixed-case">ESC</jats:styled-content>‐enriched mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s, which maintained the stem cell state.</jats:p> |
doi_str_mv | 10.1111/febs.13173 |
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imprint | Wiley, 2015 |
imprint_str_mv | Wiley, 2015 |
institution | DE-Brt1, DE-D161, DE-Zwi2, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3 |
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physical | 685-699 |
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spelling | Gao, Yuan Han, Zhuo Li, Qian Wu, Yongyan Shi, Xiaoyan Ai, Zhiying Du, Juan Li, Wenzhong Guo, Zekun Zhang, Yong 1742-464X 1742-4658 Wiley Cell Biology Molecular Biology Biochemistry http://dx.doi.org/10.1111/febs.13173 <jats:p>Micro<jats:styled-content style="fixed-case">RNA</jats:styled-content>s (mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s), a group of noncoding <jats:styled-content style="fixed-case">RNA</jats:styled-content>s, function as post‐transcriptional gene regulators and control the establishment, self‐renewal and differentiation of stem cells. Vitamin C has been recognized as a reprogramming enhancer because of its ability to induce a blastocyst‐like state in embryonic stem cells (<jats:styled-content style="fixed-case">ESC</jats:styled-content>s). However, knowledge on the regulation of mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s by vitamin C in <jats:styled-content style="fixed-case">ESC</jats:styled-content>s is limited. In this study, we found that vitamin C induced mi<jats:styled-content style="fixed-case">RNA</jats:styled-content> expression, particularly of <jats:styled-content style="fixed-case">ESC</jats:styled-content>‐specific mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s. Moreover, vitamin C maintained the mi<jats:styled-content style="fixed-case">RNA</jats:styled-content> expression of the <jats:italic>Dlk1</jats:italic>–<jats:italic>Dio3</jats:italic> imprinting region. The mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s in this region contain identical seed sequences, which target a class of genes, including <jats:italic>Kdm6b</jats:italic>,<jats:italic> Klf13</jats:italic>, and <jats:italic>Sox6</jats:italic>, and are mainly related to cell differentiation and development. These genes were significantly downregulated by vitamin C. Notably, miR‐143 promoted self‐renewal of mouse <jats:styled-content style="fixed-case">ESC</jats:styled-content>s and suppressed expression of the <jats:italic>de novo</jats:italic> methyltransferase gene <jats:italic>Dnmt3a</jats:italic>. Knockdown of miR‐143 by use of its inhibitor counteracted the vitamin C‐induced reduction in <jats:italic>Dnmt3a</jats:italic> expression, showing that vitamin C repressed <jats:italic>Dnmt3a</jats:italic> expression via miR‐143. Vitamin C also promoted <jats:styled-content style="fixed-case">DNA</jats:styled-content> demethylation, including of pluripotency gene promoters (<jats:italic>Tbx3</jats:italic>,<jats:italic> Tcl1</jats:italic>, and <jats:italic>Esrrb</jats:italic>) and <jats:styled-content style="fixed-case">ESC</jats:styled-content>‐specific mi<jats:styled-content style="fixed-case">RNA</jats:styled-content> promoters (miR‐290–295 and miR‐17–92 clusters), and <jats:styled-content style="fixed-case">DNA</jats:styled-content> hydroxymethylation, including of the intergenic differentially methylated region of the <jats:italic>Dlk1</jats:italic>–<jats:italic>Dio3</jats:italic> region. These results strongly suggested that vitamin C promoted widespread <jats:styled-content style="fixed-case">DNA</jats:styled-content> demethylation in gene promoters by modulating epigenetic modifiers, including <jats:italic>Dnmt3a</jats:italic>, which activated pluripotency genes and <jats:styled-content style="fixed-case">ESC</jats:styled-content>‐specific mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s. Then, differentiation and development genes were repressed by <jats:styled-content style="fixed-case">ESC</jats:styled-content>‐enriched mi<jats:styled-content style="fixed-case">RNA</jats:styled-content>s, which maintained the stem cell state.</jats:p> Vitamin C induces a pluripotent state in mouse embryonic stem cells by modulating micro<scp>RNA</scp> expression The FEBS Journal |
spellingShingle | Gao, Yuan, Han, Zhuo, Li, Qian, Wu, Yongyan, Shi, Xiaoyan, Ai, Zhiying, Du, Juan, Li, Wenzhong, Guo, Zekun, Zhang, Yong, The FEBS Journal, Vitamin C induces a pluripotent state in mouse embryonic stem cells by modulating microRNA expression, Cell Biology, Molecular Biology, Biochemistry |
title | Vitamin C induces a pluripotent state in mouse embryonic stem cells by modulating microRNA expression |
title_full | Vitamin C induces a pluripotent state in mouse embryonic stem cells by modulating microRNA expression |
title_fullStr | Vitamin C induces a pluripotent state in mouse embryonic stem cells by modulating microRNA expression |
title_full_unstemmed | Vitamin C induces a pluripotent state in mouse embryonic stem cells by modulating microRNA expression |
title_short | Vitamin C induces a pluripotent state in mouse embryonic stem cells by modulating microRNA expression |
title_sort | vitamin c induces a pluripotent state in mouse embryonic stem cells by modulating micro<scp>rna</scp> expression |
title_unstemmed | Vitamin C induces a pluripotent state in mouse embryonic stem cells by modulating microRNA expression |
topic | Cell Biology, Molecular Biology, Biochemistry |
url | http://dx.doi.org/10.1111/febs.13173 |