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  Network-like Impact of MicroRNAs on Neuronal Lineage Differentiation of Unrestricted Somatic Stem Cells from Human Cord Blood (USSC)

Iwaniuk, K. M., Schira, J., Weinhold, S., Jung, M., Adjaye, J., Muller, H. W., et al. (2011). Network-like Impact of MicroRNAs on Neuronal Lineage Differentiation of Unrestricted Somatic Stem Cells from Human Cord Blood (USSC). Stem Cells and Development, 20(8), 1383-1394. doi:10.1089=scd.2010.0341.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7794-C Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7795-A
Genre: Journal Article
Alternative Title : Stem Cells Dev

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 Creators:
Iwaniuk, K. M., Author
Schira, J., Author
Weinhold, S., Author
Jung, M.1, Author
Adjaye, J.2, Author              
Muller, H. W., Author
Wernet, P., Author
Trompeter, H. I., Author
Affiliations:
1Max Planck Society, ou_persistent13              
2Molecular Embryology and Aging (James Adjaye), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479654              

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 Abstract: 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.

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Language(s): eng - English
 Dates: 2011-08
 Publication Status: Published in print
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 Identifiers: eDoc: 556496
DOI: 10.1089=scd.2010.0341
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Title: Stem Cells and Development
  Alternative Title : Stem Cells Dev
Source Genre: Journal
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Pages: - Volume / Issue: 20 (8) Sequence Number: - Start / End Page: 1383 - 1394 Identifier: ISSN: 1557-8534 (Electronic)