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Factor-Reduced Human Induced Pluripotent Stem Cells Efficiently Differentiate into Neurons Independent of the Number of Reprogramming Factors
Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) by overexpression of the transcription factors OCT4, SOX2, KLF4, and c-Myc holds great promise for the development of personalized cell replacement therapies. In an attempt to minimize the risk of chromosomal disruption and t...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Hindawi Publishing Corporation
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763001/ https://www.ncbi.nlm.nih.gov/pubmed/26977154 http://dx.doi.org/10.1155/2016/4736159 |
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author | Hermann, Andreas Kim, Jeong Beom Srimasorn, Sumitra Zaehres, Holm Reinhardt, Peter Schöler, Hans R. Storch, Alexander |
author_facet | Hermann, Andreas Kim, Jeong Beom Srimasorn, Sumitra Zaehres, Holm Reinhardt, Peter Schöler, Hans R. Storch, Alexander |
author_sort | Hermann, Andreas |
collection | PubMed |
description | Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) by overexpression of the transcription factors OCT4, SOX2, KLF4, and c-Myc holds great promise for the development of personalized cell replacement therapies. In an attempt to minimize the risk of chromosomal disruption and to simplify reprogramming, several studies demonstrated that a reduced set of reprogramming factors is sufficient to generate iPSC. We recently showed that a reduction of reprogramming factors in murine cells not only reduces reprogramming efficiency but also may worsen subsequent differentiation. To prove whether this is also true for human cells, we compared the efficiency of neuronal differentiation of iPSC generated from fetal human neural stem cells with either one (OCT4; hiPSC(1F-NSC)) or two (OCT4, KLF4; hiPSC(2F-NSC)) reprogramming factors with iPSC produced from human fibroblasts using three (hiPSC(3F-FIB)) or four reprogramming factors (hiPSC(4F-FIB)). After four weeks of coculture with PA6 stromal cells, neuronal differentiation of hiPSC(1F-NSC) and hiPSC(2F-NSC) was as efficient as iPSC(3F-FIB) or iPSC(4F-FIB). We conclude that a reduction of reprogramming factors in human cells does reduce reprogramming efficiency but does not alter subsequent differentiation into neural lineages. This is of importance for the development of future application of iPSC in cell replacement therapies. |
format | Online Article Text |
id | pubmed-4763001 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-47630012016-03-14 Factor-Reduced Human Induced Pluripotent Stem Cells Efficiently Differentiate into Neurons Independent of the Number of Reprogramming Factors Hermann, Andreas Kim, Jeong Beom Srimasorn, Sumitra Zaehres, Holm Reinhardt, Peter Schöler, Hans R. Storch, Alexander Stem Cells Int Research Article Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) by overexpression of the transcription factors OCT4, SOX2, KLF4, and c-Myc holds great promise for the development of personalized cell replacement therapies. In an attempt to minimize the risk of chromosomal disruption and to simplify reprogramming, several studies demonstrated that a reduced set of reprogramming factors is sufficient to generate iPSC. We recently showed that a reduction of reprogramming factors in murine cells not only reduces reprogramming efficiency but also may worsen subsequent differentiation. To prove whether this is also true for human cells, we compared the efficiency of neuronal differentiation of iPSC generated from fetal human neural stem cells with either one (OCT4; hiPSC(1F-NSC)) or two (OCT4, KLF4; hiPSC(2F-NSC)) reprogramming factors with iPSC produced from human fibroblasts using three (hiPSC(3F-FIB)) or four reprogramming factors (hiPSC(4F-FIB)). After four weeks of coculture with PA6 stromal cells, neuronal differentiation of hiPSC(1F-NSC) and hiPSC(2F-NSC) was as efficient as iPSC(3F-FIB) or iPSC(4F-FIB). We conclude that a reduction of reprogramming factors in human cells does reduce reprogramming efficiency but does not alter subsequent differentiation into neural lineages. This is of importance for the development of future application of iPSC in cell replacement therapies. Hindawi Publishing Corporation 2016 2016-02-09 /pmc/articles/PMC4763001/ /pubmed/26977154 http://dx.doi.org/10.1155/2016/4736159 Text en Copyright © 2016 Andreas Hermann et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Hermann, Andreas Kim, Jeong Beom Srimasorn, Sumitra Zaehres, Holm Reinhardt, Peter Schöler, Hans R. Storch, Alexander Factor-Reduced Human Induced Pluripotent Stem Cells Efficiently Differentiate into Neurons Independent of the Number of Reprogramming Factors |
title | Factor-Reduced Human Induced Pluripotent Stem Cells Efficiently Differentiate into Neurons Independent of the Number of Reprogramming Factors |
title_full | Factor-Reduced Human Induced Pluripotent Stem Cells Efficiently Differentiate into Neurons Independent of the Number of Reprogramming Factors |
title_fullStr | Factor-Reduced Human Induced Pluripotent Stem Cells Efficiently Differentiate into Neurons Independent of the Number of Reprogramming Factors |
title_full_unstemmed | Factor-Reduced Human Induced Pluripotent Stem Cells Efficiently Differentiate into Neurons Independent of the Number of Reprogramming Factors |
title_short | Factor-Reduced Human Induced Pluripotent Stem Cells Efficiently Differentiate into Neurons Independent of the Number of Reprogramming Factors |
title_sort | factor-reduced human induced pluripotent stem cells efficiently differentiate into neurons independent of the number of reprogramming factors |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763001/ https://www.ncbi.nlm.nih.gov/pubmed/26977154 http://dx.doi.org/10.1155/2016/4736159 |
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