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:	Nana Wang, Xingrui Ji, Yue Wu, Shaocong Zhou, Huiyu Peng, Jingwen Wang, Shuang Yu, Jingzhong Zhang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	PD AS MSCs DA candidate transcription factors small molecules Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/71a614ffa0dd4a019dba5f12e565562a
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spelling	oai:doaj.org-article:71a614ffa0dd4a019dba5f12e565562a2021-11-25T17:53:45ZThe Different Molecular Code in Generation of Dopaminergic Neurons from Astrocytes and Mesenchymal Stem Cells10.3390/ijms2222121411422-00671661-6596https://doaj.org/article/71a614ffa0dd4a019dba5f12e565562a2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12141https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Transplantation 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.Nana WangXingrui JiYue WuShaocong ZhouHuiyu PengJingwen WangShuang YuJingzhong ZhangMDPI AGarticlePDASMSCsDA candidatetranscription factorssmall moleculesBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12141, p 12141 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PD AS MSCs DA candidate transcription factors small molecules Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	PD AS MSCs DA candidate transcription factors small molecules Biology (General) QH301-705.5 Chemistry QD1-999 Nana Wang Xingrui Ji Yue Wu Shaocong Zhou Huiyu Peng Jingwen Wang Shuang Yu Jingzhong Zhang The Different Molecular Code in Generation of Dopaminergic Neurons from Astrocytes and Mesenchymal Stem Cells
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.
format	article
author	Nana Wang Xingrui Ji Yue Wu Shaocong Zhou Huiyu Peng Jingwen Wang Shuang Yu Jingzhong Zhang
author_facet	Nana Wang Xingrui Ji Yue Wu Shaocong Zhou Huiyu Peng Jingwen Wang Shuang Yu Jingzhong Zhang
author_sort	Nana Wang
title	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_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_sort	different molecular code in generation of dopaminergic neurons from astrocytes and mesenchymal stem cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/71a614ffa0dd4a019dba5f12e565562a
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The Different Molecular Code in Generation of Dopaminergic Neurons from Astrocytes and Mesenchymal Stem Cells

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