title: Reciprocal Regulation between Bifunctional miR-9/9(∗) and its Transcriptional Modulator Notch in Human Neural Stem Cell Self-Renewal and Differentiation.
abstract: Tight regulation of the balance between self-renewal and differentiation of neural stem cells is crucial to assure proper neural development. In this context, Notch signaling is a well-known promoter of stemness. In contrast, the bifunctional brain-enriched microRNA miR-9/9(∗) has been implicated in promoting neuronal differentiation. Therefore, we set out to explore the role of both regulators in human neural stem cells. We found that miR-9/9(∗) decreases Notch activity by targeting NOTCH2 and HES1, resulting in an enhanced differentiation. Vice versa, expression levels of miR-9/9(∗) depend on the activation status of Notch signaling. While Notch inhibits differentiation of neural stem cells, it also induces miR-9/9(∗) via recruitment of the Notch intracellular domain (NICD)/RBPj transcriptional complex to the miR-9/9(∗)_2 genomic locus. Thus, our data reveal a mutual interaction between bifunctional miR-9/9(∗) and the Notch signaling cascade, calibrating the delicate balance between self-renewal and differentiation of human neural stem cells.
authors.affiliation: Institute of Reconstructive Neurobiology, LIFE & BRAIN Center, University of Bonn, 53127 Bonn, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Roese-Koerner
authors.affiliation: Institute of Reconstructive Neurobiology, LIFE & BRAIN Center, University of Bonn, 53127 Bonn, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Stappert
authors.affiliation: Institute of Reconstructive Neurobiology, LIFE & BRAIN Center, University of Bonn, 53127 Bonn, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Berger
authors.affiliation: Institute of Reconstructive Neurobiology, LIFE & BRAIN Center, University of Bonn, 53127 Bonn, Germany.
authors.forename: Nils Christian
authors.initials: NC
authors.lastname: Braun
authors.affiliation: Institute of Reconstructive Neurobiology, LIFE & BRAIN Center, University of Bonn, 53127 Bonn, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Veltel
authors.affiliation: Institute of Reconstructive Neurobiology, LIFE & BRAIN Center, University of Bonn, 53127 Bonn, Germany; DZNE, German Center for Neurodegenerative Diseases, 53127 Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Jungverdorben
authors.affiliation: Department of Neurology, University of Bonn, 53127 Bonn, Germany.
authors.forename: Bernd O
authors.initials: BO
authors.lastname: Evert
authors.affiliation: Institute of Reconstructive Neurobiology, LIFE & BRAIN Center, University of Bonn, 53127 Bonn, Germany; DZNE, German Center for Neurodegenerative Diseases, 53127 Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Peitz
authors.affiliation: Institute of Reconstructive Neurobiology, LIFE & BRAIN Center, University of Bonn, 53127 Bonn, Germany.
authors.forename: Lodovica
authors.initials: L
authors.lastname: Borghese
authors.affiliation: Institute of Reconstructive Neurobiology, LIFE & BRAIN Center, University of Bonn, 53127 Bonn, Germany; DZNE, German Center for Neurodegenerative Diseases, 53127 Bonn, Germany. Electronic address: brustle@uni-bonn.de.
authors.forename: Oliver
authors.initials: O
authors.lastname: Brüstle
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D000066673:Cell Self Renewal / Q000235:genetics*; D005786:Gene Expression Regulation; D056426:Genetic Loci; D000066449:Human Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D046912:Multiprotein Complexes; D051880:Receptors, Notch; D053829:Amyloid Precursor Protein Secretases