MicroRNA-based promotion of human neuronal differentiation and subtype specification.

MicroRNAs are key regulators of neural cell proliferation, differentiation and fate choice. Due to the limited access to human primary neural tissue, the role of microRNAs in human neuronal differentiation remains largely unknown. Here, we use a population of long-term self-renewing neuroepithelial-...

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Main Authors: Laura Stappert, Lodovica Borghese, Beate Roese-Koerner, Sandra Weinhold, Philipp Koch, Stefanie Terstegge, Markus Uhrberg, Peter Wernet, Oliver Brüstle
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3601127?pdf=render
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author Laura Stappert
Lodovica Borghese
Beate Roese-Koerner
Sandra Weinhold
Philipp Koch
Stefanie Terstegge
Markus Uhrberg
Peter Wernet
Oliver Brüstle
author_facet Laura Stappert
Lodovica Borghese
Beate Roese-Koerner
Sandra Weinhold
Philipp Koch
Stefanie Terstegge
Markus Uhrberg
Peter Wernet
Oliver Brüstle
author_sort Laura Stappert
collection DOAJ
description MicroRNAs are key regulators of neural cell proliferation, differentiation and fate choice. Due to the limited access to human primary neural tissue, the role of microRNAs in human neuronal differentiation remains largely unknown. Here, we use a population of long-term self-renewing neuroepithelial-like stem cells (lt-NES cells) derived from human embryonic stem cells to study the expression and function of microRNAs at early stages of human neural stem cell differentiation and neuronal lineage decision. Based on microRNA expression profiling followed by gain- and loss-of-function analyses in lt-NES cells and their neuronal progeny, we demonstrate that miR-153, miR-324-5p/3p and miR-181a/a contribute to the shift of lt-NES cells from self-renewal to neuronal differentiation. We further show that miR-125b and miR-181a specifically promote the generation of neurons of dopaminergic fate, whereas miR-181a inhibits the development of this neurotransmitter subtype. Our data demonstrate that time-controlled modulation of specific microRNA activities not only regulates human neural stem cell self-renewal and differentiation but also contributes to the development of defined neuronal subtypes.
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spelling doaj.art-51a637531df24406af0f692eaafe87f72022-12-22T00:46:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5901110.1371/journal.pone.0059011MicroRNA-based promotion of human neuronal differentiation and subtype specification.Laura StappertLodovica BorgheseBeate Roese-KoernerSandra WeinholdPhilipp KochStefanie TersteggeMarkus UhrbergPeter WernetOliver BrüstleMicroRNAs are key regulators of neural cell proliferation, differentiation and fate choice. Due to the limited access to human primary neural tissue, the role of microRNAs in human neuronal differentiation remains largely unknown. Here, we use a population of long-term self-renewing neuroepithelial-like stem cells (lt-NES cells) derived from human embryonic stem cells to study the expression and function of microRNAs at early stages of human neural stem cell differentiation and neuronal lineage decision. Based on microRNA expression profiling followed by gain- and loss-of-function analyses in lt-NES cells and their neuronal progeny, we demonstrate that miR-153, miR-324-5p/3p and miR-181a/a contribute to the shift of lt-NES cells from self-renewal to neuronal differentiation. We further show that miR-125b and miR-181a specifically promote the generation of neurons of dopaminergic fate, whereas miR-181a inhibits the development of this neurotransmitter subtype. Our data demonstrate that time-controlled modulation of specific microRNA activities not only regulates human neural stem cell self-renewal and differentiation but also contributes to the development of defined neuronal subtypes.http://europepmc.org/articles/PMC3601127?pdf=render
spellingShingle Laura Stappert
Lodovica Borghese
Beate Roese-Koerner
Sandra Weinhold
Philipp Koch
Stefanie Terstegge
Markus Uhrberg
Peter Wernet
Oliver Brüstle
MicroRNA-based promotion of human neuronal differentiation and subtype specification.
PLoS ONE
title MicroRNA-based promotion of human neuronal differentiation and subtype specification.
title_full MicroRNA-based promotion of human neuronal differentiation and subtype specification.
title_fullStr MicroRNA-based promotion of human neuronal differentiation and subtype specification.
title_full_unstemmed MicroRNA-based promotion of human neuronal differentiation and subtype specification.
title_short MicroRNA-based promotion of human neuronal differentiation and subtype specification.
title_sort microrna based promotion of human neuronal differentiation and subtype specification
url http://europepmc.org/articles/PMC3601127?pdf=render
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