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Conversion of T cells to B cells by inactivation of polycomb-mediated epigenetic suppression of the B-lineage program
In general, cell fate is determined primarily by transcription factors, followed by epigenetic mechanisms fixing the status. While the importance of transcription factors controlling cell fate has been well characterized, epigenetic regulation of cell fate maintenance remains to be elucidated. Here...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159663/ https://www.ncbi.nlm.nih.gov/pubmed/27913604 http://dx.doi.org/10.1101/gad.290593.116 |
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author | Ikawa, Tomokatsu Masuda, Kyoko Endo, Takaho A. Endo, Mitsuhiro Isono, Kyoichi Koseki, Yoko Nakagawa, Rinako Kometani, Kohei Takano, Junichiro Agata, Yasutoshi Katsura, Yoshimoto Kurosaki, Tomohiro Vidal, Miguel Koseki, Haruhiko Kawamoto, Hiroshi |
author_facet | Ikawa, Tomokatsu Masuda, Kyoko Endo, Takaho A. Endo, Mitsuhiro Isono, Kyoichi Koseki, Yoko Nakagawa, Rinako Kometani, Kohei Takano, Junichiro Agata, Yasutoshi Katsura, Yoshimoto Kurosaki, Tomohiro Vidal, Miguel Koseki, Haruhiko Kawamoto, Hiroshi |
author_sort | Ikawa, Tomokatsu |
collection | PubMed |
description | In general, cell fate is determined primarily by transcription factors, followed by epigenetic mechanisms fixing the status. While the importance of transcription factors controlling cell fate has been well characterized, epigenetic regulation of cell fate maintenance remains to be elucidated. Here we provide an obvious fate conversion case, in which the inactivation of polycomb-medicated epigenetic regulation results in conversion of T-lineage progenitors to the B-cell fate. In T-cell-specific Ring1A/B-deficient mice, T-cell development was severely blocked at an immature stage. We found that these developmentally arrested T-cell precursors gave rise to functional B cells upon transfer to immunodeficient mice. We further demonstrated that the arrest was almost completely canceled by additional deletion of Pax5. These results indicate that the maintenance of T-cell fate critically requires epigenetic suppression of the B-lineage gene program. |
format | Online Article Text |
id | pubmed-5159663 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-51596632017-05-15 Conversion of T cells to B cells by inactivation of polycomb-mediated epigenetic suppression of the B-lineage program Ikawa, Tomokatsu Masuda, Kyoko Endo, Takaho A. Endo, Mitsuhiro Isono, Kyoichi Koseki, Yoko Nakagawa, Rinako Kometani, Kohei Takano, Junichiro Agata, Yasutoshi Katsura, Yoshimoto Kurosaki, Tomohiro Vidal, Miguel Koseki, Haruhiko Kawamoto, Hiroshi Genes Dev Research Paper In general, cell fate is determined primarily by transcription factors, followed by epigenetic mechanisms fixing the status. While the importance of transcription factors controlling cell fate has been well characterized, epigenetic regulation of cell fate maintenance remains to be elucidated. Here we provide an obvious fate conversion case, in which the inactivation of polycomb-medicated epigenetic regulation results in conversion of T-lineage progenitors to the B-cell fate. In T-cell-specific Ring1A/B-deficient mice, T-cell development was severely blocked at an immature stage. We found that these developmentally arrested T-cell precursors gave rise to functional B cells upon transfer to immunodeficient mice. We further demonstrated that the arrest was almost completely canceled by additional deletion of Pax5. These results indicate that the maintenance of T-cell fate critically requires epigenetic suppression of the B-lineage gene program. Cold Spring Harbor Laboratory Press 2016-11-15 /pmc/articles/PMC5159663/ /pubmed/27913604 http://dx.doi.org/10.1101/gad.290593.116 Text en © 2016 Ikawa et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Paper Ikawa, Tomokatsu Masuda, Kyoko Endo, Takaho A. Endo, Mitsuhiro Isono, Kyoichi Koseki, Yoko Nakagawa, Rinako Kometani, Kohei Takano, Junichiro Agata, Yasutoshi Katsura, Yoshimoto Kurosaki, Tomohiro Vidal, Miguel Koseki, Haruhiko Kawamoto, Hiroshi Conversion of T cells to B cells by inactivation of polycomb-mediated epigenetic suppression of the B-lineage program |
title | Conversion of T cells to B cells by inactivation of polycomb-mediated epigenetic suppression of the B-lineage program |
title_full | Conversion of T cells to B cells by inactivation of polycomb-mediated epigenetic suppression of the B-lineage program |
title_fullStr | Conversion of T cells to B cells by inactivation of polycomb-mediated epigenetic suppression of the B-lineage program |
title_full_unstemmed | Conversion of T cells to B cells by inactivation of polycomb-mediated epigenetic suppression of the B-lineage program |
title_short | Conversion of T cells to B cells by inactivation of polycomb-mediated epigenetic suppression of the B-lineage program |
title_sort | conversion of t cells to b cells by inactivation of polycomb-mediated epigenetic suppression of the b-lineage program |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159663/ https://www.ncbi.nlm.nih.gov/pubmed/27913604 http://dx.doi.org/10.1101/gad.290593.116 |
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