Abstract
Neural stem cells (NSC) with self-renewal and multipotent properties serve as an ideal cell source for transplantation to treat neurodegenerative insults such as Parkinson's disease. We used Agilent's and Illumina Whole Human Genome Oligonucleotide Microarray to compare the genomic profiles of human embryonic NSC at a single time point in culture, and a multicellular tissue from postmortem adult substantia nigra (SN) which are rich in dopaminergic (DA) neurons. We identified 13525 up-regulated genes in both cell types of which 3737 (27.6%) genes were up-regulated in the hENSC, 4116 (30.4%) genes were up-regulated in the human substantia nigra dopaminergic cells, and 5672 (41.93%) were significantly up-regulated in both cell population. Careful analysis of the data that emerged using DAVID has permitted us to distinguish several genes and pathways that are involved in dopaminergic (DA) differentiation, and to identify the crucial signaling pathways that direct the process of differentiation. The set of genes expressed more highly at hENSC is enriched in molecules known or predicted to be involved in the M phase of the mitotic cell cycle. On the other hand, the genes enriched in SN cells include a different set of functional categories, namely synaptic transmission, central nervous system development, structural constituents of the myelin sheath, the internode region of axons, myelination, cell projection, cell somata, ion transport, and the voltage-gated ion channel complex. Our results were also compared with data from various databases, and between different types of arrays, Agilent versus Illumina. This approach has allowed us to confirm the consistency of our obtained results for a large number of genes that delineate the phenotypical differences of embryonic NSCs, and SN cells.
Highlights
The adult central nervous system (CNS) has a limited capacity to regenerate new neurons, in the substantia nigra, spinal cord, and cortex [1]
As representatives of dopaminergic neurons, we had included five RNA samples collected from normal human brain that are known to be rich in dopaminergic neurons
Based on previous characterization by Invitrogen, the human neural stem cells used in the present study were self-renewing, multipotent stem cells of the nervous system derived from the NIH approved H9 (WA09) human embryonic stem cells
Summary
The adult CNS has a limited capacity to regenerate new neurons, in the substantia nigra, spinal cord, and cortex [1]. The embryonic human neural stem cells (NSC) are multipotent cells that have been derived from human embryonic stem cells as well as isolated from fetal tissues [3], [4]. Such cells are viewed as a possible source of neurons for a cell-based therapy of neurodegenerative disorders, such as Parkinson’s disease (PD). Transcription factors like Nurr1 [5] and Pitx3 [10] were introduced into stem cells to enhance the the proof-of- principle for developing different types of allogenic neurons including personalized DA neurons for replacement therapy in PD
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