Transcription Profiling of Adult and Fetal Human Neuroprogenitors Identifies Divergent Paths to Maintain the Neuroprogenitor Cell State

Abstract

Global gene expression profiling was performed using RNA from adult human hippocampus-derived neuroprogenitor cells (NPCs) and multipotent frontal cortical fetal NPCs compared with adult human mesenchymal stem cells (hMSCs) as a multipotent adult stem cell control, and adult human hippocampal tissue, to define a gene expression pattern that is specific for human NPCs. The results were compared with data from various databases. Hierarchical cluster analysis of all neuroectodermal cell/tissue types revealed a strong relationship of adult hippocampal NPCs with various white matter tissues, whereas fetal NPCs strongly correlate with fetal brain tissue. However, adult and fetal NPCs share the expression of a variety of genes known to be related to signal transduction, cell metabolism and neuroectodermal tissue. In contrast, adult NPCs and hMSCs overlap in the expression of genes mainly involved in extracellular matrix biology. We present for the first time a detailed transcriptome analysis of human adult NPCs suggesting a relationship between hippocampal NPCs and white matter-derived precursor cells. We further provide a framework for standardized comparative gene expression analysis of human brain-derived NPCs with other stem cell populations or differentiated tissues.

Gene Expression Profiling of Embryonic Human Neural Stem Cells and Dopaminergic Neurons from Adult Human Substantia Nigra

“…In the present study, PMP2, PMP22 and MOG were up-regulated to 10.17, 4.43, and 9.70 fold respectively in SN neurons while they were not detected in hENSC. Interestingly, in contrast to the findings of Maisel et al [48] CD44 and GDF1/LASS1 were not expressed in our hNSCs samples. Such finding might point to unrestricted stem cell potential of our examined hENSC line in contrast to adult NPC where CD44 and GDF1/LASS1 were overexpressed [48].…”

“…These findings were in harmony with that of Maisel et al [48] who demonstrated that a number of genes specific for neurons were transcribed only on reduced levels in different neuroprogenitors cells such as the 25-kDa synaptosome-associated protein (SNAP25), and neurogranin (NRGN).…”

“…Hierarchical clustering of adult NPCs and tissues containing mainly white matter, such as spinal cord and corpus callosum, is characterized by a strong expression of MHCII genes and myelin components such as peripheral myelin protein two (PMP2), myelin-associated glycoprotein (MAG), or the myelin-oligodendrocyte glycoprotein (MOG) [48]. In the present study, PMP2, PMP22 and MOG were up-regulated to 10.17, 4.43, and 9.70 fold respectively in SN neurons while they were not detected in hENSC.…”

A new role for the P2Y-like GPR17 receptor in the modulation of multipotency of oligodendrocyte precursor cells in vitro

“…In this respect, we have recently focused our attention on the possible role exerted by the P2Y-like receptor GPR17, which is closely related to both purinergic P2Y and CysLT receptors [16]. Notably, GPR17 is one of the three genes differentially expressed by human adult hippocampal precursor cells when compared to embryonic stem cells [17]. We and others have demonstrated that GPR17 is transiently expressed at specific differentiation stages of OPCs, undergoes a tightly regulated modulation to drive OPC maturation towards fully mature oligodendrocytes, and contributes to their reaction to harmful conditions [18][19][20][21][22].…”

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“…This extracellular matrix protein gene is known to be expressed by both adult neuroprogenitors and mesenchymal stem cells. 37 When looking at neural cell lineage markers, three (CD44, NCAN1 and OPRS1) out of five markers were upregulated, S100B showed no change and TUBB3 was downregulated (Table 1). Reverse transcription-PCR analysis further confirmed that NSC1 cells did not express pluripotent stem cell markers Oct-4 and Nanog, mesoderm marker Brachyury T and endoderm marker AFP (Figure 1d).…”