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Heterokaryon-Based Reprogramming of Human B Lymphocytes for Pluripotency Requires Oct4 but Not Sox2
Differentiated cells can be reprogrammed through the formation of heterokaryons and hybrid cells when fused with embryonic stem (ES) cells. Here, we provide evidence that conversion of human B-lymphocytes towards a multipotent state is initiated much more rapidly than previously thought, occurring i...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527997/ https://www.ncbi.nlm.nih.gov/pubmed/18773085 http://dx.doi.org/10.1371/journal.pgen.1000170 |
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author | Pereira, Carlos F. Terranova, Rémi Ryan, Natalie K. Santos, Joana Morris, Kelly J. Cui, Wei Merkenschlager, Matthias Fisher, Amanda G. |
author_facet | Pereira, Carlos F. Terranova, Rémi Ryan, Natalie K. Santos, Joana Morris, Kelly J. Cui, Wei Merkenschlager, Matthias Fisher, Amanda G. |
author_sort | Pereira, Carlos F. |
collection | PubMed |
description | Differentiated cells can be reprogrammed through the formation of heterokaryons and hybrid cells when fused with embryonic stem (ES) cells. Here, we provide evidence that conversion of human B-lymphocytes towards a multipotent state is initiated much more rapidly than previously thought, occurring in transient heterokaryons before nuclear fusion and cell division. Interestingly, reprogramming of human lymphocytes by mouse ES cells elicits the expression of a human ES-specific gene profile, in which markers of human ES cells are expressed (hSSEA4, hFGF receptors and ligands), but markers that are specific to mouse ES cells are not (e.g., Bmp4 and LIF receptor). Using genetically engineered mouse ES cells, we demonstrate that successful reprogramming of human lymphocytes is independent of Sox2, a factor thought to be required for induced pluripotent stem (iPS) cells. In contrast, there is a distinct requirement for Oct4 in the establishment but not the maintenance of the reprogrammed state. Experimental heterokaryons, therefore, offer a powerful approach to trace the contribution of individual factors to the reprogramming of human somatic cells towards a multipotent state. |
format | Text |
id | pubmed-2527997 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-25279972008-09-05 Heterokaryon-Based Reprogramming of Human B Lymphocytes for Pluripotency Requires Oct4 but Not Sox2 Pereira, Carlos F. Terranova, Rémi Ryan, Natalie K. Santos, Joana Morris, Kelly J. Cui, Wei Merkenschlager, Matthias Fisher, Amanda G. PLoS Genet Research Article Differentiated cells can be reprogrammed through the formation of heterokaryons and hybrid cells when fused with embryonic stem (ES) cells. Here, we provide evidence that conversion of human B-lymphocytes towards a multipotent state is initiated much more rapidly than previously thought, occurring in transient heterokaryons before nuclear fusion and cell division. Interestingly, reprogramming of human lymphocytes by mouse ES cells elicits the expression of a human ES-specific gene profile, in which markers of human ES cells are expressed (hSSEA4, hFGF receptors and ligands), but markers that are specific to mouse ES cells are not (e.g., Bmp4 and LIF receptor). Using genetically engineered mouse ES cells, we demonstrate that successful reprogramming of human lymphocytes is independent of Sox2, a factor thought to be required for induced pluripotent stem (iPS) cells. In contrast, there is a distinct requirement for Oct4 in the establishment but not the maintenance of the reprogrammed state. Experimental heterokaryons, therefore, offer a powerful approach to trace the contribution of individual factors to the reprogramming of human somatic cells towards a multipotent state. Public Library of Science 2008-09-05 /pmc/articles/PMC2527997/ /pubmed/18773085 http://dx.doi.org/10.1371/journal.pgen.1000170 Text en Pereira et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Pereira, Carlos F. Terranova, Rémi Ryan, Natalie K. Santos, Joana Morris, Kelly J. Cui, Wei Merkenschlager, Matthias Fisher, Amanda G. Heterokaryon-Based Reprogramming of Human B Lymphocytes for Pluripotency Requires Oct4 but Not Sox2 |
title | Heterokaryon-Based Reprogramming of Human B Lymphocytes for Pluripotency Requires Oct4 but Not Sox2 |
title_full | Heterokaryon-Based Reprogramming of Human B Lymphocytes for Pluripotency Requires Oct4 but Not Sox2 |
title_fullStr | Heterokaryon-Based Reprogramming of Human B Lymphocytes for Pluripotency Requires Oct4 but Not Sox2 |
title_full_unstemmed | Heterokaryon-Based Reprogramming of Human B Lymphocytes for Pluripotency Requires Oct4 but Not Sox2 |
title_short | Heterokaryon-Based Reprogramming of Human B Lymphocytes for Pluripotency Requires Oct4 but Not Sox2 |
title_sort | heterokaryon-based reprogramming of human b lymphocytes for pluripotency requires oct4 but not sox2 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527997/ https://www.ncbi.nlm.nih.gov/pubmed/18773085 http://dx.doi.org/10.1371/journal.pgen.1000170 |
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