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Journal Article

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

MPS-Authors

Jung,  M.
Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50054

Adjaye,  J.
Molecular Embryology and Aging (James Adjaye), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Iwaniuk.pdf
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Citation

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.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0010-7794-C
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.