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Transcription Factor-Based Strategies to Generate Neural Cell Types from Human Pluripotent Stem Cells

Canals, Isaac LU ; Quist, Ella LU orcid and Ahlenius, Henrik LU (2021) In Cellular Reprogramming 23(4). p.206-220
Abstract

In the last years, the use of pluripotent stem cells in studies of human biology has grown exponentially. These cells represent an infinite source for differentiation into several human cell types facilitating the investigation on biological processes, functionality of cells, or diseases mechanisms in relevant human models. In the neurobiology field, pluripotent stem cells have been extensively used to generate the main neuronal and glial cells of the brain. Traditionally, protocols following developmental cues have been applied to pluripotent stem cells to drive differentiation toward different cell lineages; however, these protocols give rise to populations with mixed identities. Interestingly, new protocols applying overexpression of... (More)

In the last years, the use of pluripotent stem cells in studies of human biology has grown exponentially. These cells represent an infinite source for differentiation into several human cell types facilitating the investigation on biological processes, functionality of cells, or diseases mechanisms in relevant human models. In the neurobiology field, pluripotent stem cells have been extensively used to generate the main neuronal and glial cells of the brain. Traditionally, protocols following developmental cues have been applied to pluripotent stem cells to drive differentiation toward different cell lineages; however, these protocols give rise to populations with mixed identities. Interestingly, new protocols applying overexpression of lineage-specific transcription factors (TFs) have emerged and facilitated the generation of highly pure populations of specific subtypes of neurons and glial cells in an easy, reproducible, and rapid manner. In this study, we review protocols based on this strategy to generate excitatory, inhibitory, dopaminergic, and motor neurons as well as astrocytes, oligodendrocytes, and microglia. In addition, we will discuss the main applications for cells generated with these protocols, including disease modeling, drug screening, and mechanistic studies. Finally, we will discuss the advantages and disadvantages of TF-based protocols and present our view of the future in this field.

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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
astrocytes, microglia, neurons, oligodendrocytes, pluripotent stem cells, reprogramming
in
Cellular Reprogramming
volume
23
issue
4
pages
15 pages
publisher
Mary Ann Liebert, Inc.
external identifiers
  • pmid:34388027
  • scopus:85113173856
ISSN
2152-4971
DOI
10.1089/cell.2021.0045
language
English
LU publication?
yes
id
b359c0ad-70e0-42b5-b9e6-e07b056c3ed4
date added to LUP
2021-09-06 16:14:50
date last changed
2024-04-06 08:23:53
@article{b359c0ad-70e0-42b5-b9e6-e07b056c3ed4,
  abstract     = {{<p>In the last years, the use of pluripotent stem cells in studies of human biology has grown exponentially. These cells represent an infinite source for differentiation into several human cell types facilitating the investigation on biological processes, functionality of cells, or diseases mechanisms in relevant human models. In the neurobiology field, pluripotent stem cells have been extensively used to generate the main neuronal and glial cells of the brain. Traditionally, protocols following developmental cues have been applied to pluripotent stem cells to drive differentiation toward different cell lineages; however, these protocols give rise to populations with mixed identities. Interestingly, new protocols applying overexpression of lineage-specific transcription factors (TFs) have emerged and facilitated the generation of highly pure populations of specific subtypes of neurons and glial cells in an easy, reproducible, and rapid manner. In this study, we review protocols based on this strategy to generate excitatory, inhibitory, dopaminergic, and motor neurons as well as astrocytes, oligodendrocytes, and microglia. In addition, we will discuss the main applications for cells generated with these protocols, including disease modeling, drug screening, and mechanistic studies. Finally, we will discuss the advantages and disadvantages of TF-based protocols and present our view of the future in this field.</p>}},
  author       = {{Canals, Isaac and Quist, Ella and Ahlenius, Henrik}},
  issn         = {{2152-4971}},
  keywords     = {{astrocytes; microglia; neurons; oligodendrocytes; pluripotent stem cells; reprogramming}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{206--220}},
  publisher    = {{Mary Ann Liebert, Inc.}},
  series       = {{Cellular Reprogramming}},
  title        = {{Transcription Factor-Based Strategies to Generate Neural Cell Types from Human Pluripotent Stem Cells}},
  url          = {{http://dx.doi.org/10.1089/cell.2021.0045}},
  doi          = {{10.1089/cell.2021.0045}},
  volume       = {{23}},
  year         = {{2021}},
}