Direct Reprogramming of Mouse Fibroblasts to Neural Stem Cells by Small Molecules
Although it is possible to generate neural stem cells (NSC) from somatic cells by reprogramming technologies with transcription factors, clinical utilization of patient-specific NSC for the treatment of human diseases remains elusive. The risk hurdles are associated with viral transduction vectors i...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2016/4304916 |
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| author | Yan-Chuang Han Yoon Lim Michael D. Duffieldl Hua Li Jia Liu Nimshitha Pavathuparambil Abdul Manaph Miao Yang Damien J. Keating Xin-Fu Zhou |
| author_facet | Yan-Chuang Han Yoon Lim Michael D. Duffieldl Hua Li Jia Liu Nimshitha Pavathuparambil Abdul Manaph Miao Yang Damien J. Keating Xin-Fu Zhou |
| author_sort | Yan-Chuang Han |
| collection | DOAJ |
| description | Although it is possible to generate neural stem cells (NSC) from somatic cells by reprogramming technologies with transcription factors, clinical utilization of patient-specific NSC for the treatment of human diseases remains elusive. The risk hurdles are associated with viral transduction vectors induced mutagenesis, tumor formation from undifferentiated stem cells, and transcription factors-induced genomic instability. Here we describe a viral vector-free and more efficient method to induce mouse fibroblasts into NSC using small molecules. The small molecule-induced neural stem (SMINS) cells closely resemble NSC in morphology, gene expression patterns, self-renewal, excitability, and multipotency. Furthermore, the SMINS cells are able to differentiate into astrocytes, functional neurons, and oligodendrocytes in vitro and in vivo. Thus, we have established a novel way to efficiently induce neural stem cells (iNSC) from fibroblasts using only small molecules without altering the genome. Such chemical induction removes the risks associated with current techniques such as the use of viral vectors or the induction of oncogenic factors. This technique may, therefore, enable NSC to be utilized in various applications within clinical medicine. |
| format | Article |
| id | doaj-art-5184d4b06e26440f81df74040a6c610c |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-5184d4b06e26440f81df74040a6c610c2025-02-03T01:28:39ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/43049164304916Direct Reprogramming of Mouse Fibroblasts to Neural Stem Cells by Small MoleculesYan-Chuang Han0Yoon Lim1Michael D. Duffieldl2Hua Li3Jia Liu4Nimshitha Pavathuparambil Abdul Manaph5Miao Yang6Damien J. Keating7Xin-Fu Zhou8School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5000, AustraliaSchool of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5000, AustraliaDepartment of Human Physiology and Centre for Neuroscience, Flinders University of South Australia, P.O. Box 2100, Adelaide, SA 5001, AustraliaSchool of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5000, AustraliaSchool of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5000, AustraliaSchool of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5000, AustraliaSchool of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5000, AustraliaDepartment of Human Physiology and Centre for Neuroscience, Flinders University of South Australia, P.O. Box 2100, Adelaide, SA 5001, AustraliaSchool of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5000, AustraliaAlthough it is possible to generate neural stem cells (NSC) from somatic cells by reprogramming technologies with transcription factors, clinical utilization of patient-specific NSC for the treatment of human diseases remains elusive. The risk hurdles are associated with viral transduction vectors induced mutagenesis, tumor formation from undifferentiated stem cells, and transcription factors-induced genomic instability. Here we describe a viral vector-free and more efficient method to induce mouse fibroblasts into NSC using small molecules. The small molecule-induced neural stem (SMINS) cells closely resemble NSC in morphology, gene expression patterns, self-renewal, excitability, and multipotency. Furthermore, the SMINS cells are able to differentiate into astrocytes, functional neurons, and oligodendrocytes in vitro and in vivo. Thus, we have established a novel way to efficiently induce neural stem cells (iNSC) from fibroblasts using only small molecules without altering the genome. Such chemical induction removes the risks associated with current techniques such as the use of viral vectors or the induction of oncogenic factors. This technique may, therefore, enable NSC to be utilized in various applications within clinical medicine.http://dx.doi.org/10.1155/2016/4304916 |
| spellingShingle | Yan-Chuang Han Yoon Lim Michael D. Duffieldl Hua Li Jia Liu Nimshitha Pavathuparambil Abdul Manaph Miao Yang Damien J. Keating Xin-Fu Zhou Direct Reprogramming of Mouse Fibroblasts to Neural Stem Cells by Small Molecules Stem Cells International |
| title | Direct Reprogramming of Mouse Fibroblasts to Neural Stem Cells by Small Molecules |
| title_full | Direct Reprogramming of Mouse Fibroblasts to Neural Stem Cells by Small Molecules |
| title_fullStr | Direct Reprogramming of Mouse Fibroblasts to Neural Stem Cells by Small Molecules |
| title_full_unstemmed | Direct Reprogramming of Mouse Fibroblasts to Neural Stem Cells by Small Molecules |
| title_short | Direct Reprogramming of Mouse Fibroblasts to Neural Stem Cells by Small Molecules |
| title_sort | direct reprogramming of mouse fibroblasts to neural stem cells by small molecules |
| url | http://dx.doi.org/10.1155/2016/4304916 |
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