Direct Reprogramming of Human Fetal- and Stem Cell-Derived Glial Progenitor Cells into Midbrain Dopaminergic Neurons
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Direct Reprogramming of Human Fetal- and Stem Cell-Derived Glial Progenitor Cells into Midbrain Dopaminergic Neurons. / Nolbrant, Sara; Giacomoni, Jessica; Hoban, Deirdre B.; Bruzelius, Andreas; Birtele, Marcella; Chandler-Militello, Devin; Pereira, Maria; Ottosson, Daniella Rylander; Goldman, Steven A.; Parmar, Malin.
In: Stem Cell Reports, Vol. 15, No. 4, 2020, p. 869-882.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Direct Reprogramming of Human Fetal- and Stem Cell-Derived Glial Progenitor Cells into Midbrain Dopaminergic Neurons
AU - Nolbrant, Sara
AU - Giacomoni, Jessica
AU - Hoban, Deirdre B.
AU - Bruzelius, Andreas
AU - Birtele, Marcella
AU - Chandler-Militello, Devin
AU - Pereira, Maria
AU - Ottosson, Daniella Rylander
AU - Goldman, Steven A.
AU - Parmar, Malin
N1 - Publisher Copyright: © 2020 The Authors
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - dopaminergic neurons
KW - glial progenitor cells
KW - hESC
KW - neuronal reprogramming
KW - Parkinson's disease
U2 - 10.1016/j.stemcr.2020.08.013
DO - 10.1016/j.stemcr.2020.08.013
M3 - Journal article
C2 - 32976765
AN - SCOPUS:85092148719
VL - 15
SP - 869
EP - 882
JO - Stem Cell Reports
JF - Stem Cell Reports
SN - 2213-6711
IS - 4
ER -
ID: 269517958