dc.contributor.author
Kutsche, Lisa K.
dc.contributor.author
Gysi, Deisy M.
dc.contributor.author
Fallmann, Joerg
dc.contributor.author
Lenk, Kerstin
dc.contributor.author
Petri, Rebecca
dc.contributor.author
Swiersy, Anka
dc.contributor.author
Klapper, Simon D.
dc.contributor.author
Pircs, Karolina
dc.contributor.author
Khattak, Shahryar
dc.contributor.author
Stadler, Peter F.
dc.contributor.author
Jakobsson, Johan
dc.contributor.author
Nowick, Katja
dc.contributor.author
Busskamp, Volker
dc.date.accessioned
2018-11-15T10:31:30Z
dc.date.available
2018-11-15T10:31:30Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/23206
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-998
dc.description.abstract
Non-coding RNAs regulate many biological processes including neurogenesis. The brain-enriched miR-124 has been assigned as a key player of neuronal differentiation via its complex but little understood regulation of thousands of annotated targets. To systematically chart its regulatory functions, we used CRISPR/Cas9 gene editing to disrupt all six miR-124 alleles in human induced pluripotent stem cells. Upon neuronal induction, miR-124-deleted cells underwent neurogenesis and became functional neurons, albeit with altered morphology and neurotransmitter specification. Using RNA-induced-silencing-complex precipitation, we identified 98 high-confidence miR-124 targets, of which some directly led to decreased viability. By performing advanced transcription-factor-network analysis, we identified indirect miR-124 effects on apoptosis, neuronal subtype differentiation, and the regulation of previously uncharacterized zinc finger transcription factors. Our data emphasize the need for combined experimental- and system-level analyses to comprehensively disentangle and reveal miRNA functions, including their involvement in the neurogenesis of diverse neuronal cell types found in the human brain.
en
dc.format.extent
24 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
systems biology
de
dc.subject
miRNA regulation
en
dc.subject
miRNA dynamics
en
dc.subject
miR-124 targetome
en
dc.subject
gene regulatory network analysis
en
dc.subject
miRNA-transcription factor networks
en
dc.subject
neuronal miRNAs
en
dc.subject
AGO2-RIP-seq
de
dc.subject
euronal differentiation from human stem cells
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::611 Menschliche Anatomie, Zytologie, Histologie
dc.title
Combined Experimental and System-Level Analyses Reveal the Complex Regulatory Network of miR-124 during Human Neurogenesis
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1016/j.cels.2018.08.011
dcterms.bibliographicCitation.journaltitle
Cell Systems
dcterms.bibliographicCitation.number
4
dcterms.bibliographicCitation.pagestart
438
dcterms.bibliographicCitation.pageend
452
dcterms.bibliographicCitation.volume
7
dcterms.bibliographicCitation.url
https://doi.org/10.1016/j.cels.2018.08.011
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation.other
Institut für Biologie
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refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.issn
2405-4712