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Myc-regulated microRNAs attenuate embryonic stem cell differentiation
Myc proteins are known to have an important function in stem cell maintenance. As Myc has been shown earlier to regulate microRNAs (miRNAs) involved in proliferation, we sought to determine whether c-Myc also affects embryonic stem (ES) cell maintenance and differentiation through miRNAs. Using a qu...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744176/ https://www.ncbi.nlm.nih.gov/pubmed/19745813 http://dx.doi.org/10.1038/emboj.2009.254 |
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author | Lin, Chin-Hsing Jackson, Aimee L Guo, Jie Linsley, Peter S Eisenman, Robert N |
author_facet | Lin, Chin-Hsing Jackson, Aimee L Guo, Jie Linsley, Peter S Eisenman, Robert N |
author_sort | Lin, Chin-Hsing |
collection | PubMed |
description | Myc proteins are known to have an important function in stem cell maintenance. As Myc has been shown earlier to regulate microRNAs (miRNAs) involved in proliferation, we sought to determine whether c-Myc also affects embryonic stem (ES) cell maintenance and differentiation through miRNAs. Using a quantitative primer-extension PCR assay we identified miRNAs, including, miR-141, miR-200, and miR-429 whose expression is regulated by c-Myc in ES cells, but not in the differentiated and tumourigenic derivatives of ES cells. Chromatin immunoprecipitation analyses indicate that in ES cells c-Myc binds proximal to genomic regions encoding the induced miRNAs. We used expression profiling and seed homology to identify genes specifically downregulated both by these miRNAs and by c-Myc. We further show that the introduction of c-Myc-induced miRNAs into murine ES cells significantly attenuates the downregulation of pluripotency markers on induction of differentiation after withdrawal of the ES cell maintenance factor LIF. In contrast, knockdown of the endogenous miRNAs accelerate differentiation. Our data show that in ES cells c-Myc acts, in part, through a subset of miRNAs to attenuate differentiation. |
format | Text |
id | pubmed-2744176 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-27441762009-09-16 Myc-regulated microRNAs attenuate embryonic stem cell differentiation Lin, Chin-Hsing Jackson, Aimee L Guo, Jie Linsley, Peter S Eisenman, Robert N EMBO J Article Myc proteins are known to have an important function in stem cell maintenance. As Myc has been shown earlier to regulate microRNAs (miRNAs) involved in proliferation, we sought to determine whether c-Myc also affects embryonic stem (ES) cell maintenance and differentiation through miRNAs. Using a quantitative primer-extension PCR assay we identified miRNAs, including, miR-141, miR-200, and miR-429 whose expression is regulated by c-Myc in ES cells, but not in the differentiated and tumourigenic derivatives of ES cells. Chromatin immunoprecipitation analyses indicate that in ES cells c-Myc binds proximal to genomic regions encoding the induced miRNAs. We used expression profiling and seed homology to identify genes specifically downregulated both by these miRNAs and by c-Myc. We further show that the introduction of c-Myc-induced miRNAs into murine ES cells significantly attenuates the downregulation of pluripotency markers on induction of differentiation after withdrawal of the ES cell maintenance factor LIF. In contrast, knockdown of the endogenous miRNAs accelerate differentiation. Our data show that in ES cells c-Myc acts, in part, through a subset of miRNAs to attenuate differentiation. Nature Publishing Group 2009-10-21 2009-09-10 /pmc/articles/PMC2744176/ /pubmed/19745813 http://dx.doi.org/10.1038/emboj.2009.254 Text en Copyright © 2009, European Molecular Biology Organization http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission. |
spellingShingle | Article Lin, Chin-Hsing Jackson, Aimee L Guo, Jie Linsley, Peter S Eisenman, Robert N Myc-regulated microRNAs attenuate embryonic stem cell differentiation |
title | Myc-regulated microRNAs attenuate embryonic stem cell differentiation |
title_full | Myc-regulated microRNAs attenuate embryonic stem cell differentiation |
title_fullStr | Myc-regulated microRNAs attenuate embryonic stem cell differentiation |
title_full_unstemmed | Myc-regulated microRNAs attenuate embryonic stem cell differentiation |
title_short | Myc-regulated microRNAs attenuate embryonic stem cell differentiation |
title_sort | myc-regulated micrornas attenuate embryonic stem cell differentiation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744176/ https://www.ncbi.nlm.nih.gov/pubmed/19745813 http://dx.doi.org/10.1038/emboj.2009.254 |
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