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The Different Molecular Code in Generation of Dopaminergic Neurons from Astrocytes and Mesenchymal Stem Cells

Transplantation of exogenous dopaminergic (DA) neurons is an alternative strategy to replenish DA neurons that have lost along the course of Parkinson’s disease (PD). From the perspective of ethical acceptation, the source limitations, and the intrinsic features of PD pathology, astrocytes (AS) and...

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Autores principales: Wang, Nana, Ji, Xingrui, Wu, Yue, Zhou, Shaocong, Peng, Huiyu, Wang, Jingwen, Yu, Shuang, Zhang, Jingzhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8622032/
https://www.ncbi.nlm.nih.gov/pubmed/34830023
http://dx.doi.org/10.3390/ijms222212141
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author Wang, Nana
Ji, Xingrui
Wu, Yue
Zhou, Shaocong
Peng, Huiyu
Wang, Jingwen
Yu, Shuang
Zhang, Jingzhong
author_facet Wang, Nana
Ji, Xingrui
Wu, Yue
Zhou, Shaocong
Peng, Huiyu
Wang, Jingwen
Yu, Shuang
Zhang, Jingzhong
author_sort Wang, Nana
collection PubMed
description Transplantation of exogenous dopaminergic (DA) neurons is an alternative strategy to replenish DA neurons that have lost along the course of Parkinson’s disease (PD). From the perspective of ethical acceptation, the source limitations, and the intrinsic features of PD pathology, astrocytes (AS) and mesenchymal stem cells (MSCs) are the two promising candidates of DA induction. In the present study, we induced AS or MSCs primary culture by the combination of the classical transcription-factor cocktails Mash1, Lmx1a, and Nurr1 (MLN), the chemical cocktails (S/C/D), and the morphogens SHH, FGF8, and FGF2 (S/F8/F2); the efficiency of induction into DA neurons was further analyzed by using immunostaining against the DA neuronal markers. AS could be efficiently converted into the DA neurons in vitro by the transcriptional regulation of MLN, and the combination with S/C/D or S/F8/F2 further increased the conversion efficiency. In contrast, MSCs from umbilical cord (UC-MSCs) or adipose tissue (AD-MSCs) showed moderate TH immunoreactivity after the induction with S/F8/F2 instead of with MLN or S/C/D. Our data demonstrated that AS and MSCs held lineage-specific molecular codes on the induction into DA neurons and highlighted the unique superiority of AS in the potential of cell replacement therapy for PD.
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spelling pubmed-86220322021-11-27 The Different Molecular Code in Generation of Dopaminergic Neurons from Astrocytes and Mesenchymal Stem Cells Wang, Nana Ji, Xingrui Wu, Yue Zhou, Shaocong Peng, Huiyu Wang, Jingwen Yu, Shuang Zhang, Jingzhong Int J Mol Sci Article Transplantation of exogenous dopaminergic (DA) neurons is an alternative strategy to replenish DA neurons that have lost along the course of Parkinson’s disease (PD). From the perspective of ethical acceptation, the source limitations, and the intrinsic features of PD pathology, astrocytes (AS) and mesenchymal stem cells (MSCs) are the two promising candidates of DA induction. In the present study, we induced AS or MSCs primary culture by the combination of the classical transcription-factor cocktails Mash1, Lmx1a, and Nurr1 (MLN), the chemical cocktails (S/C/D), and the morphogens SHH, FGF8, and FGF2 (S/F8/F2); the efficiency of induction into DA neurons was further analyzed by using immunostaining against the DA neuronal markers. AS could be efficiently converted into the DA neurons in vitro by the transcriptional regulation of MLN, and the combination with S/C/D or S/F8/F2 further increased the conversion efficiency. In contrast, MSCs from umbilical cord (UC-MSCs) or adipose tissue (AD-MSCs) showed moderate TH immunoreactivity after the induction with S/F8/F2 instead of with MLN or S/C/D. Our data demonstrated that AS and MSCs held lineage-specific molecular codes on the induction into DA neurons and highlighted the unique superiority of AS in the potential of cell replacement therapy for PD. MDPI 2021-11-09 /pmc/articles/PMC8622032/ /pubmed/34830023 http://dx.doi.org/10.3390/ijms222212141 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Nana
Ji, Xingrui
Wu, Yue
Zhou, Shaocong
Peng, Huiyu
Wang, Jingwen
Yu, Shuang
Zhang, Jingzhong
The Different Molecular Code in Generation of Dopaminergic Neurons from Astrocytes and Mesenchymal Stem Cells
title The Different Molecular Code in Generation of Dopaminergic Neurons from Astrocytes and Mesenchymal Stem Cells
title_full The Different Molecular Code in Generation of Dopaminergic Neurons from Astrocytes and Mesenchymal Stem Cells
title_fullStr The Different Molecular Code in Generation of Dopaminergic Neurons from Astrocytes and Mesenchymal Stem Cells
title_full_unstemmed The Different Molecular Code in Generation of Dopaminergic Neurons from Astrocytes and Mesenchymal Stem Cells
title_short The Different Molecular Code in Generation of Dopaminergic Neurons from Astrocytes and Mesenchymal Stem Cells
title_sort different molecular code in generation of dopaminergic neurons from astrocytes and mesenchymal stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8622032/
https://www.ncbi.nlm.nih.gov/pubmed/34830023
http://dx.doi.org/10.3390/ijms222212141
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