Histone H3K27me3 demethylases KDM6A and KDM6B modulate definitive endoderm differentiation from human ESCs by regulating WNT signaling pathway
Definitive endoderm differentiation is crucial for generating respiratory and gastrointestinal organs including pancreas and liver. However, whether epigenetic regulation contributes to this process is unknown. Here, we show that the H3K27me3 demethylases KDM6A and KDM6B play an important role in en...
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| Published in | Cell research Vol. 23; no. 1; pp. 122 - 130 |
|---|---|
| Main Authors | , , |
| Format | Journal Article |
| Language | English |
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Nature Publishing Group UK
01.01.2013
Nature Publishing Group |
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| Online Access | Get full text |
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| Abstract | Definitive endoderm differentiation is crucial for generating respiratory and gastrointestinal organs including pancreas and liver. However, whether epigenetic regulation contributes to this process is unknown. Here, we show that the H3K27me3 demethylases KDM6A and KDM6B play an important role in endoderm differentiation from human ESCs. Knockdown of KDM6A or KDM6B impairs endoderm differentiation, which can be rescued by sequential treatment with WNT agonist and antagonist. KDM6A and KDM6B contribute to the activation of WNT3 and DKK1 at different differentiation stages when WNT3 and DKK1 are required for mesendoderm and definitive en- doderm differentiation, respectively. Our study not only uncovers an important role of the H3K27me3 demethylases in definitive endoderm differentiation, but also reveals that they achieve this through modulating the WNT signaling pathway. |
|---|---|
| AbstractList | Definitive endoderm differentiation is crucial for generating respiratory and
gastrointestinal organs including pancreas and liver. However, whether epigenetic
regulation contributes to this process is unknown. Here, we show that the H3K27me3
demethylases KDM6A and KDM6B play an important role in endoderm differentiation from human
ESCs. Knockdown of KDM6A or KDM6B impairs endoderm differentiation, which can be rescued
by sequential treatment with WNT agonist and antagonist. KDM6A and KDM6B contribute to the
activation of WNT3 and DKK1 at different differentiation stages when WNT3 and DKK1 are
required for mesendoderm and definitive endoderm differentiation, respectively. Our study
not only uncovers an important role of the H3K27me3 demethylases in definitive endoderm
differentiation, but also reveals that they achieve this through modulating the WNT
signaling pathway. Definitive endoderm differentiation is crucial for generating respiratory and gastrointestinal organs including pancreas and liver. However, whether epigenetic regulation contributes to this process is unknown. Here, we show that the H3K27me3 demethylases KDM6A and KDM6B play an important role in endoderm differentiation from human ESCs. Knockdown of KDM6A or KDM6B impairs endoderm differentiation, which can be rescued by sequential treatment with WNT agonist and antagonist. KDM6A and KDM6B contribute to the activation of WNT3 and DKK1 at different differentiation stages when WNT3 and DKK1 are required for mesendoderm and definitive endoderm differentiation, respectively. Our study not only uncovers an important role of the H3K27me3 demethylases in definitive endoderm differentiation, but also reveals that they achieve this through modulating the WNT signaling pathway. Definitive endoderm differentiation is crucial for generating respiratory and gastrointestinal organs including pancreas and liver. However, whether epigenetic regulation contributes to this process is unknown. Here, we show that the H3K27me3 demethylases KDM6A and KDM6B play an important role in endoderm differentiation from human ESCs. Knockdown of KDM6A or KDM6B impairs endoderm differentiation, which can be rescued by sequential treatment with WNT agonist and antagonist. KDM6A and KDM6B contribute to the activation of WNT3 and DKK1 at different differentiation stages when WNT3 and DKK1 are required for mesendoderm and definitive en- doderm differentiation, respectively. Our study not only uncovers an important role of the H3K27me3 demethylases in definitive endoderm differentiation, but also reveals that they achieve this through modulating the WNT signaling pathway. Definitive endoderm differentiation is crucial for generating respiratory and gastrointestinal organs including pancreas and liver. However, whether epigenetic regulation contributes to this process is unknown. Here, we show that the H3K27me3 demethylases KDM6A and KDM6B play an important role in endoderm differentiation from human ESCs. Knockdown of KDM6A or KDM6B impairs endoderm differentiation, which can be rescued by sequential treatment with WNT agonist and antagonist. KDM6A and KDM6B contribute to the activation of WNT3 and DKK1 at different differentiation stages when WNT3 and DKK1 are required for mesendoderm and definitive endoderm differentiation, respectively. Our study not only uncovers an important role of the H3K27me3 demethylases in definitive endoderm differentiation, but also reveals that they achieve this through modulating the WNT signaling pathway.Definitive endoderm differentiation is crucial for generating respiratory and gastrointestinal organs including pancreas and liver. However, whether epigenetic regulation contributes to this process is unknown. Here, we show that the H3K27me3 demethylases KDM6A and KDM6B play an important role in endoderm differentiation from human ESCs. Knockdown of KDM6A or KDM6B impairs endoderm differentiation, which can be rescued by sequential treatment with WNT agonist and antagonist. KDM6A and KDM6B contribute to the activation of WNT3 and DKK1 at different differentiation stages when WNT3 and DKK1 are required for mesendoderm and definitive endoderm differentiation, respectively. Our study not only uncovers an important role of the H3K27me3 demethylases in definitive endoderm differentiation, but also reveals that they achieve this through modulating the WNT signaling pathway. |
| Author | Wei Jiang Jinzhao Wang Yi Zhang |
| AuthorAffiliation | Howard Hughes Medical Institute, Chevy Chase, Maryland 20815-6789, USA Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill NC 27599-7295, USA |
| Author_xml | – sequence: 1 givenname: Wei surname: Jiang fullname: Jiang, Wei organization: Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill – sequence: 2 givenname: Jinzhao surname: Wang fullname: Wang, Jinzhao organization: Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill – sequence: 3 givenname: Yi surname: Zhang fullname: Zhang, Yi email: yi_zhang@med.unc.edu organization: Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/22907667$$D View this record in MEDLINE/PubMed |
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| Notes | KDM6A/KDM6B; definitive endoderm differentiation; WNT pathway regulation 31-1568/Q Definitive endoderm differentiation is crucial for generating respiratory and gastrointestinal organs including pancreas and liver. However, whether epigenetic regulation contributes to this process is unknown. Here, we show that the H3K27me3 demethylases KDM6A and KDM6B play an important role in endoderm differentiation from human ESCs. Knockdown of KDM6A or KDM6B impairs endoderm differentiation, which can be rescued by sequential treatment with WNT agonist and antagonist. KDM6A and KDM6B contribute to the activation of WNT3 and DKK1 at different differentiation stages when WNT3 and DKK1 are required for mesendoderm and definitive en- doderm differentiation, respectively. Our study not only uncovers an important role of the H3K27me3 demethylases in definitive endoderm differentiation, but also reveals that they achieve this through modulating the WNT signaling pathway. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
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| Snippet | Definitive endoderm differentiation is crucial for generating respiratory and gastrointestinal organs including pancreas and liver. However, whether epigenetic... Definitive endoderm differentiation is crucial for generating respiratory and gastrointestinal organs including pancreas and liver. However, whether epigenetic... |
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| SubjectTerms | 631/136/142 631/208/200 631/80/86 Biomedical and Life Sciences Cell Biology Cell Differentiation Cell Line Embryonic Stem Cells - cytology Embryonic Stem Cells - metabolism Endoderm - cytology Endoderm - metabolism Histone Demethylases - antagonists & inhibitors Histone Demethylases - genetics Histone Demethylases - metabolism Histones - genetics Histones - metabolism Humans Intercellular Signaling Peptides and Proteins - metabolism Jumonji Domain-Containing Histone Demethylases - antagonists & inhibitors Jumonji Domain-Containing Histone Demethylases - genetics Jumonji Domain-Containing Histone Demethylases - metabolism Life Sciences Methylation Nuclear Proteins - antagonists & inhibitors Nuclear Proteins - genetics Nuclear Proteins - metabolism Original original-article RNA Interference RNA, Small Interfering - metabolism Up-Regulation WNT Wnt Signaling Pathway Wnt3 Protein - agonists Wnt3 Protein - antagonists & inhibitors Wnt3 Protein - metabolism 人类胚胎干细胞 信号转导通路 分化阶段 受体激动剂 组蛋白 胚层 调制 |
| Title | Histone H3K27me3 demethylases KDM6A and KDM6B modulate definitive endoderm differentiation from human ESCs by regulating WNT signaling pathway |
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