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

Nolbrant, Sara LU ; Giacomoni, Jessica LU ; Hoban, Deirdre LU ; Bruzelius, Andreas LU ; Birtele, Marcella LU orcid ; Chandler-Militello, Devin ; Pereira, Maria LU ; Ottosson, Daniella Rylander LU ; Goldman, Steven A. and Parmar, Malin LU orcid (2020) In Stem Cell Reports 15(4). p.869-882
Abstract
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... (More)
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. (Less)
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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Stem Cell Reports
volume
15
issue
4
pages
869 - 882
publisher
Cell Press
external identifiers
  • pmid:32976765
  • scopus:85092148719
  • pmid:32976765
ISSN
2213-6711
DOI
10.1016/j.stemcr.2020.08.013
language
English
LU publication?
yes
additional info
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
id
2ec98338-79dd-4747-bbfa-7c3186ba6174
date added to LUP
2020-09-28 08:34:32
date last changed
2024-04-03 11:49:35
@article{2ec98338-79dd-4747-bbfa-7c3186ba6174,
  abstract     = {{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.}},
  author       = {{Nolbrant, Sara and Giacomoni, Jessica and Hoban, Deirdre and Bruzelius, Andreas and Birtele, Marcella and Chandler-Militello, Devin and Pereira, Maria and Ottosson, Daniella Rylander and Goldman, Steven A. and Parmar, Malin}},
  issn         = {{2213-6711}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{869--882}},
  publisher    = {{Cell Press}},
  series       = {{Stem Cell Reports}},
  title        = {{Direct Reprogramming of Human Fetal- and Stem Cell-Derived Glial Progenitor Cells into Midbrain Dopaminergic Neurons}},
  url          = {{https://lup.lub.lu.se/search/files/101167473/Stem_Cell_Reports._2020_Sep_Nolbrant.pdf}},
  doi          = {{10.1016/j.stemcr.2020.08.013}},
  volume       = {{15}},
  year         = {{2020}},
}