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Reprogramming somatic cells to cells with neuronal characteristics by defined medium both in vitro and in vivo

BACKGROUND: Currently, direct conversion from somatic cells to neurons requires virus-mediated delivery of at least one transcriptional factor or a combination of several small-molecule compounds. Delivery of transcriptional factors may affect genome stability, while small-molecule compounds may req...

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Autores principales: He, Songwei, Guo, Yiping, Zhang, Yixin, Li, Yuan, Feng, Chengqian, Li, Xiang, Lin, Lilong, Guo, Lin, Wang, Haitao, Liu, Chunhua, Zheng, Yi, Luo, Chuanming, Liu, Qiang, Wang, Fuhui, Sun, Hao, Liang, Lining, Li, Lingyu, Su, Huanxing, Chen, Jiekai, Pei, Duanqing, Zheng, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696146/
https://www.ncbi.nlm.nih.gov/pubmed/26719791
http://dx.doi.org/10.1186/s13619-015-0027-6
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author He, Songwei
Guo, Yiping
Zhang, Yixin
Li, Yuan
Feng, Chengqian
Li, Xiang
Lin, Lilong
Guo, Lin
Wang, Haitao
Liu, Chunhua
Zheng, Yi
Luo, Chuanming
Liu, Qiang
Wang, Fuhui
Sun, Hao
Liang, Lining
Li, Lingyu
Su, Huanxing
Chen, Jiekai
Pei, Duanqing
Zheng, Hui
author_facet He, Songwei
Guo, Yiping
Zhang, Yixin
Li, Yuan
Feng, Chengqian
Li, Xiang
Lin, Lilong
Guo, Lin
Wang, Haitao
Liu, Chunhua
Zheng, Yi
Luo, Chuanming
Liu, Qiang
Wang, Fuhui
Sun, Hao
Liang, Lining
Li, Lingyu
Su, Huanxing
Chen, Jiekai
Pei, Duanqing
Zheng, Hui
author_sort He, Songwei
collection PubMed
description BACKGROUND: Currently, direct conversion from somatic cells to neurons requires virus-mediated delivery of at least one transcriptional factor or a combination of several small-molecule compounds. Delivery of transcriptional factors may affect genome stability, while small-molecule compounds may require more evaluations when applied in vivo. Thus, a defined medium with only conventional growth factors or additives for cell culture is desirable for inducing neuronal trans-differentiation. RESULTS: Here, we report that a defined medium (5C) consisting of basic fibroblast growth factor (bFGF), N2 supplement, leukemia inhibitory factor, vitamin C (Vc), and β-mercaptoethanol (βMe) induces the direct conversion of somatic cells to cells with neuronal characteristics. Application of 5C medium converted mouse embryonic fibroblasts (MEFs) into TuJ+ neuronal-like cells, which were capable of survival after being transplanted into the mouse brain. The same 5C medium could convert primary rat astrocytes into neuronal-like cells with mature electrophysiology characteristics in vitro and facilitated the recovery of brain injury, possibly by inducing similar conversions, when infused into the mouse brain in vivo. Crucially, 5C medium could also induce neuronal characteristics in several human cell types. CONCLUSIONS: In summary, this 5C medium not only provides a means to derive cells with neuronal characteristics without viral transfection in vitro but might also be useful to produce neurons in vivo for neurodegenerative disease treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13619-015-0027-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-46961462015-12-31 Reprogramming somatic cells to cells with neuronal characteristics by defined medium both in vitro and in vivo He, Songwei Guo, Yiping Zhang, Yixin Li, Yuan Feng, Chengqian Li, Xiang Lin, Lilong Guo, Lin Wang, Haitao Liu, Chunhua Zheng, Yi Luo, Chuanming Liu, Qiang Wang, Fuhui Sun, Hao Liang, Lining Li, Lingyu Su, Huanxing Chen, Jiekai Pei, Duanqing Zheng, Hui Cell Regen Research Article BACKGROUND: Currently, direct conversion from somatic cells to neurons requires virus-mediated delivery of at least one transcriptional factor or a combination of several small-molecule compounds. Delivery of transcriptional factors may affect genome stability, while small-molecule compounds may require more evaluations when applied in vivo. Thus, a defined medium with only conventional growth factors or additives for cell culture is desirable for inducing neuronal trans-differentiation. RESULTS: Here, we report that a defined medium (5C) consisting of basic fibroblast growth factor (bFGF), N2 supplement, leukemia inhibitory factor, vitamin C (Vc), and β-mercaptoethanol (βMe) induces the direct conversion of somatic cells to cells with neuronal characteristics. Application of 5C medium converted mouse embryonic fibroblasts (MEFs) into TuJ+ neuronal-like cells, which were capable of survival after being transplanted into the mouse brain. The same 5C medium could convert primary rat astrocytes into neuronal-like cells with mature electrophysiology characteristics in vitro and facilitated the recovery of brain injury, possibly by inducing similar conversions, when infused into the mouse brain in vivo. Crucially, 5C medium could also induce neuronal characteristics in several human cell types. CONCLUSIONS: In summary, this 5C medium not only provides a means to derive cells with neuronal characteristics without viral transfection in vitro but might also be useful to produce neurons in vivo for neurodegenerative disease treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13619-015-0027-6) contains supplementary material, which is available to authorized users. BioMed Central 2015-12-30 /pmc/articles/PMC4696146/ /pubmed/26719791 http://dx.doi.org/10.1186/s13619-015-0027-6 Text en © He et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
He, Songwei
Guo, Yiping
Zhang, Yixin
Li, Yuan
Feng, Chengqian
Li, Xiang
Lin, Lilong
Guo, Lin
Wang, Haitao
Liu, Chunhua
Zheng, Yi
Luo, Chuanming
Liu, Qiang
Wang, Fuhui
Sun, Hao
Liang, Lining
Li, Lingyu
Su, Huanxing
Chen, Jiekai
Pei, Duanqing
Zheng, Hui
Reprogramming somatic cells to cells with neuronal characteristics by defined medium both in vitro and in vivo
title Reprogramming somatic cells to cells with neuronal characteristics by defined medium both in vitro and in vivo
title_full Reprogramming somatic cells to cells with neuronal characteristics by defined medium both in vitro and in vivo
title_fullStr Reprogramming somatic cells to cells with neuronal characteristics by defined medium both in vitro and in vivo
title_full_unstemmed Reprogramming somatic cells to cells with neuronal characteristics by defined medium both in vitro and in vivo
title_short Reprogramming somatic cells to cells with neuronal characteristics by defined medium both in vitro and in vivo
title_sort reprogramming somatic cells to cells with neuronal characteristics by defined medium both in vitro and in vivo
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696146/
https://www.ncbi.nlm.nih.gov/pubmed/26719791
http://dx.doi.org/10.1186/s13619-015-0027-6
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