Direct Reprogramming of Human Fetal- and Stem Cell-Derived Glial Progenitor Cells into Midbrain Dopaminergic Neurons.

Autor:	Nolbrant S; Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, and Lund Stem Cell Centre, Department of Experimental Medical Science, Lund University, Lund, Sweden., Giacomoni J; Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, and Lund Stem Cell Centre, Department of Experimental Medical Science, Lund University, Lund, Sweden., Hoban DB; Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, and Lund Stem Cell Centre, Department of Experimental Medical Science, Lund University, Lund, Sweden., Bruzelius A; Regenerative Neurophysiology, Wallenberg Neuroscience Center, Lund Stem Cell Center, Department of Experimental Medical Science, Lund University, Lund, Sweden., Birtele M; Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, and Lund Stem Cell Centre, Department of Experimental Medical Science, Lund University, Lund, Sweden., Chandler-Militello D; Center for Translational Neuromedicine and Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA., Pereira M; Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, and Lund Stem Cell Centre, Department of Experimental Medical Science, Lund University, Lund, Sweden., Ottosson DR; Regenerative Neurophysiology, Wallenberg Neuroscience Center, Lund Stem Cell Center, Department of Experimental Medical Science, Lund University, Lund, Sweden., Goldman SA; Center for Translational Neuromedicine and Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA; Center for Neuroscience, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, Denmark; Neuroscience Center, Rigshospitalet, Copenhagen, Denmark., Parmar M; Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, and Lund Stem Cell Centre, Department of Experimental Medical Science, Lund University, Lund, Sweden. Electronic address: malin.parmar@med.lu.se.
Jazyk:	angličtina
Zdroj:	Stem cell reports [Stem Cell Reports] 2020 Oct 13; Vol. 15 (4), pp. 869-882. Date of Electronic Publication: 2020 Sep 24.
DOI:	10.1016/j.stemcr.2020.08.013
Abstrakt:	Human glial progenitor cells (hGPCs) are promising cellular substrates to explore for the in situ production of new neurons for brain repair. Proof of concept for direct neuronal reprogramming of glial progenitors has been obtained in mouse models in vivo, but conversion using human cells has not yet been demonstrated. Such studies have been difficult to perform since hGPCs are born late during human fetal development, with limited accessibility for in vitro culture. In this study, we show proof of concept of hGPC conversion using fetal cells and also establish a renewable and reproducible stem cell-based hGPC system for direct neural conversion in vitro. Using this system, we have identified optimal combinations of fate determinants for the efficient dopaminergic (DA) conversion of hGPCs, thereby yielding a therapeutically relevant cell type that selectively degenerates in Parkinson's disease. The induced DA neurons show a progressive, subtype-specific phenotypic maturation and acquire functional electrophysiological properties indicative of DA phenotype. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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