title: MicroRNA-based promotion of human neuronal differentiation and subtype specification.
abstract: 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.
authors.affiliation: Institute of Reconstructive Neurobiology, LIFE & BRAIN Center, University of Bonn, Bonn, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Stappert
authors.forename: Lodovica
authors.initials: L
authors.lastname: Borghese
authors.forename: Beate
authors.initials: B
authors.lastname: Roese-Koerner
authors.forename: Sandra
authors.initials: S
authors.lastname: Weinhold
authors.forename: Philipp
authors.initials: P
authors.lastname: Koch
authors.forename: Stefanie
authors.initials: S
authors.lastname: Terstegge
authors.forename: Markus
authors.initials: M
authors.lastname: Uhrberg
authors.forename: Peter
authors.initials: P
authors.lastname: Wernet
authors.forename: Oliver
authors.initials: O
authors.lastname: Brüstle
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D035683:MicroRNAs