Abstract
Global gene expression profiling was performed using RNA from human embryonic neural stem cells (hENSC), and adult human olfactory bulb-derived neural stem cells (OBNSCs), to define a gene expression pattern and signaling pathways that are specific for each cell lineage. We have demonstrated large differences in the gene expression profile of human embryonic NSC, and adult human OBNSCs, but less variability between parallel cultures. Transcripts of genes involved in neural tube development and patterning (ALDH1A2, FOXA2), progenitor marker genes (LMX1a, ALDH1A1, SOX10), proliferation of neural progenitors (WNT1 and WNT3a), neuroplastin (NPTN), POU3F1 (OCT6), neuroligin (NLGN4X), MEIS2, and NPAS1 were up-regulated in both cell populations. By Gene Ontology, 325 out of 3875 investigated gene sets were scientifically different. 41 out of the 307 investigated Cellular Component (CC) categories, 45 out of the 620 investigated Molecular Function (MF) categories, and 239 out of the 2948 investigated Biological Process (BP) categories were significant. KEGG Pathway Class Comparison had revealed that 75 out of 171 investigated gene sets passed the 0.005 significance threshold. Levels of gene expression were explored in three signaling pathways, Notch, Wnt, and mTOR that are known to be involved in NS cell fates determination. The transcriptional signature also deciphers the role of genes involved in epigenetic modifications. SWI/SNF DNA chromatin remodeling complex family, including SMARCC1 and SMARCE1, were found specifically up-regulated in our OBNSC but not in hENSC. Differences in gene expression profile of transcripts controlling epigenetic modifications, and signaling pathways might indicate differences in the therapeutic potential of our examined two cell populations in relation to in cell survival, proliferation, migration, and differentiation following engraftments in different CNS insults.
Highlights
Multipotent neural stem cells (NSC) that are capable of selfrenewal and generate all three cell types of the central nervous system are presently the research hotspot in neuroscience
We focus on comparing the genomic profiles and signal pathway analysis of human adult olfactory bulb and embryonic NSCs using oligonucleotide microarrays and immunocytochemistry to provide a). knowledge of the gene expression profiles and alternative signaling pathways of adult human OB-NSC, and whether adult human OB-NSCs are identical to the embryonic ones; b). to determine how the gene expression patterns of a adult OB-NSCs change and whether its potency becomes narrowed in comparison to embryonic ones, and c. to clarify possible epigenetic alteration between the two cell classes
90% of the cells stained positive for the undifferentiated NSC marker nestin, SOX2 and the proliferation marker Ki67 (Figure 1A, B)
Summary
Multipotent neural stem cells (NSC) that are capable of selfrenewal and generate all three cell types of the central nervous system (neurons, oligodendrocytes, and astrocytes) are presently the research hotspot in neuroscience. There is a great interest and potential of adult human olfactory bulb NSC (OBNSC) in cell replacement therapy, there is lack of data about their gene expression profiling, and molecular pathways that govern their multipotency, proliferation, migration, and signaling mechanisms.
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