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          Institute: MPI für molekulare Genetik     Collection: Department of Vertebrate Genomics     Display Documents

ID: 556496.0, MPI für molekulare Genetik / Department of Vertebrate Genomics
Network-like Impact of MicroRNAs on Neuronal Lineage Differentiation of Unrestricted Somatic Stem Cells from Human Cord Blood (USSC)
Authors:Iwaniuk, K. M.; Schira, J.; Weinhold, S.; Jung, M.; Adjaye, J.; Muller, H. W.; Wernet, P.; Trompeter, H. I.
Date of Publication (YYYY-MM-DD):2011-08
Title of Journal:Stem Cells and Development
Journal Abbrev.:Stem Cells Dev
Issue / Number:8
Start Page:1383
End Page:1394
Copyright:© 2011 Mary Ann Liebert, Inc., publishers
Review Status:not specified
Audience:Experts Only
Abstract / Description:Unrestricted somatic stem cells (USSC) represent an intrinsically multipotent CD45-negative population from human cord blood. They show differentiation into neuronal cells of a dopaminergic phenotype which express neuronal markers like synaptophysin, neuronal-specific nuclear protein (NeuN), and neurofilament and release the neurotransmitter dopamine accompanied by expression of dopaminergic key factors tyrosine hydroxylase and Nurr1 (NR4A2). MicroRNA expression analysis revealed downregulation of a set of 18 microRNAs during neuronal lineage differentiation of USSC, including members of the miR-17-92 family and additional microRNAs like miR-130a, -138, -218, and -335. In-silico target gene predictions for this microRNA group uncovered a large set of proteins involved in neuronal differentiation a strong impact on differentiation-related pathways like Axon Guidance, TGFss-, WNT-, and MAPK-Signaling. Experimental target validations confirmed approximately 35% of predictions tested and revealed a group of proteins with specific impact in neuronal differentiation and function including neurobeachin (NBEA), neurogenic differentiation 1 (NEUROD1), cysteine-rich motor neuron protein 1 (CRIM1), neuropentraxin 1 (NPTX1), and others. These proteins are combined targets for several subgroups from the set of 18 downregulated microRNAs. This finding was further supported by the observed upregulation of a significant amount of predicted and validated target genes based on Illumina Beadstudio microarray data. Confirming the functional relationship of a limited panel of microRNAs and predicted target proteins reveals a clear network-like impact of the group of 18 downregulated microRNAs on proteins with functions involved in neuronal development and function.
Comment of the Author/Creator:E-mail: peter.wernet@uni-duesseldorf.de
External Publication Status:published
Document Type:Article
Communicated by:Hans Lehrach
Affiliations:MPI für molekulare Genetik
External Affiliations:Medical Faculty, University Düsseldorf, Institute for Transplantation Diagnostics and Cell Therapeutics, Düsseldorf, Germany
Molecular Neurobiology Laboratory, Department of Neurology, Medical Faculty, University Düsseldorf, Düsseldorf, Germany
Identifiers:ISSN:1557-8534 (Electronic) [ID No:1]
DOI:10.1089=scd.2010.0341 [ID No:2]
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