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Small molecular compounds efficiently convert human fibroblasts directly into neurons

No effective treatment is currently available for neurodegenerative diseases, and existing pharmacotherapy is inconsistent with severe side effects. Cell replacement therapy is promising for neurodegenerative disease treatment, and the induction of neurons is an unmet need for such therapy. The pres...

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Autores principales: Yang, Jijuan, Cao, Huimei, Guo, Shengnan, Zhu, Hong, Tao, Hong, Zhang, Linna, Chen, Zhangping, Sun, Tao, Chi, Shuhong, Hu, Qikuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646904/
https://www.ncbi.nlm.nih.gov/pubmed/33174059
http://dx.doi.org/10.3892/mmr.2020.11559
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author Yang, Jijuan
Cao, Huimei
Guo, Shengnan
Zhu, Hong
Tao, Hong
Zhang, Linna
Chen, Zhangping
Sun, Tao
Chi, Shuhong
Hu, Qikuan
author_facet Yang, Jijuan
Cao, Huimei
Guo, Shengnan
Zhu, Hong
Tao, Hong
Zhang, Linna
Chen, Zhangping
Sun, Tao
Chi, Shuhong
Hu, Qikuan
author_sort Yang, Jijuan
collection PubMed
description No effective treatment is currently available for neurodegenerative diseases, and existing pharmacotherapy is inconsistent with severe side effects. Cell replacement therapy is promising for neurodegenerative disease treatment, and the induction of neurons is an unmet need for such therapy. The present study investigated the potential of a combined medium composed of conditioned medium and eight small molecular compounds in reprogramming human foreskin fibroblasts (HFFs) into neurons. HFFs were cultured from foreskin and then induced by small molecules to generate neurons. The results demonstrated that the conditioned medium containing forskolin, RepSox, SP600125, CHIR99021, Go6983, Y-27632, IXS9 and I-BET151 effectively induced human fibroblasts to change into neurons in vitro. Following a 30-day induction, the cells exhibited neuronal properties as determined by morphological and phenotypical alterations. The induced cells exhibited expression of neuronal markers, including class III β-tubulin, microtubule-associated protein 2, vesicular glutamate transporter 1 and γ-aminobutyric acid, accompanied by increased expression of neuronal transcription factors, including neuronal differentiation 1 and achaete-scute family bHLH transcription factor 1, and decreased expression levels of fibroblast-specific genes. Furthermore, these cells also exhibited electrophysiological properties of neurons. Notably, the course of cell morphological alterations demonstrated the differentiation of fibroblasts into neurons. The present study provided a novel combination of existing small molecular compounds that efficiently reprogramed human fibroblasts into neurons.
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spelling pubmed-76469042020-11-13 Small molecular compounds efficiently convert human fibroblasts directly into neurons Yang, Jijuan Cao, Huimei Guo, Shengnan Zhu, Hong Tao, Hong Zhang, Linna Chen, Zhangping Sun, Tao Chi, Shuhong Hu, Qikuan Mol Med Rep Articles No effective treatment is currently available for neurodegenerative diseases, and existing pharmacotherapy is inconsistent with severe side effects. Cell replacement therapy is promising for neurodegenerative disease treatment, and the induction of neurons is an unmet need for such therapy. The present study investigated the potential of a combined medium composed of conditioned medium and eight small molecular compounds in reprogramming human foreskin fibroblasts (HFFs) into neurons. HFFs were cultured from foreskin and then induced by small molecules to generate neurons. The results demonstrated that the conditioned medium containing forskolin, RepSox, SP600125, CHIR99021, Go6983, Y-27632, IXS9 and I-BET151 effectively induced human fibroblasts to change into neurons in vitro. Following a 30-day induction, the cells exhibited neuronal properties as determined by morphological and phenotypical alterations. The induced cells exhibited expression of neuronal markers, including class III β-tubulin, microtubule-associated protein 2, vesicular glutamate transporter 1 and γ-aminobutyric acid, accompanied by increased expression of neuronal transcription factors, including neuronal differentiation 1 and achaete-scute family bHLH transcription factor 1, and decreased expression levels of fibroblast-specific genes. Furthermore, these cells also exhibited electrophysiological properties of neurons. Notably, the course of cell morphological alterations demonstrated the differentiation of fibroblasts into neurons. The present study provided a novel combination of existing small molecular compounds that efficiently reprogramed human fibroblasts into neurons. D.A. Spandidos 2020-12 2020-10-02 /pmc/articles/PMC7646904/ /pubmed/33174059 http://dx.doi.org/10.3892/mmr.2020.11559 Text en Copyright: © Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Yang, Jijuan
Cao, Huimei
Guo, Shengnan
Zhu, Hong
Tao, Hong
Zhang, Linna
Chen, Zhangping
Sun, Tao
Chi, Shuhong
Hu, Qikuan
Small molecular compounds efficiently convert human fibroblasts directly into neurons
title Small molecular compounds efficiently convert human fibroblasts directly into neurons
title_full Small molecular compounds efficiently convert human fibroblasts directly into neurons
title_fullStr Small molecular compounds efficiently convert human fibroblasts directly into neurons
title_full_unstemmed Small molecular compounds efficiently convert human fibroblasts directly into neurons
title_short Small molecular compounds efficiently convert human fibroblasts directly into neurons
title_sort small molecular compounds efficiently convert human fibroblasts directly into neurons
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646904/
https://www.ncbi.nlm.nih.gov/pubmed/33174059
http://dx.doi.org/10.3892/mmr.2020.11559
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