Transcriptomics

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Identification of a neuronal gene expression signature: Role of cell-cycle arrest in murine neuronal differentiation in vitro


ABSTRACT: Stem cells are a potential key strategy for treating neurodegenerative diseases in which the generation of new neurons is critical. A better understanding of the characteristics and molecular properties of neural stem cells (NSC) and differentiated neurons can help in assessing neuronal maturity and possibly in devising better therapeutic strategies. We have therefore performed an in-depth gene expression profiling study of the C17.2 NSC line and primary neurons (PN) derived from embryonic mouse brains. Microarray analysis revealed a neuron-specific gene expression signature that distinguishes PN from NSCs, with elevated levels of transcripts involved in neuronal functions such as neurite development, axon guidance, in PN. The same comparison revealed decreased levels of multiple cytokine transcripts such as IFN, TNF, TGF, and IL. Among the differentially expressed genes, we found a statistically significant enrichment of genes in the ephrin, neurotrophin, CDK5 and actin pathways which control multiple neuronal-specific functions. Furthermore, genes involved in cell cycle were among the most significantly changed in PN. In order to better understand the role of cell cycle arrest in mediating NSCs differentiation, we blocked the cell cycle of NSCs with Mitomycin C (MMC) and examined cellular morphology and gene expression signatures. Although these MMC-treated NSCs displayed a neuronal morphology and expressed some neuronal differentiation marker genes, their gene expression patterns was very different from primary neurons. We conclude that: 1) Fully differentiated primary neurons display a specific neuronal gene expression signature; 2) cell-cycle block in NSC does not induce the formation of fully differentiated neurons; 3) Cytokines such as IFN, TNF, TGF and IL are part of normal NSC function and/or physiology; 4) Signaling pathways of ephrin, neurotrophin, CDK5 and actin, related to major neuronal features, are dynamically enriched in genes showing changes in expression level. Gene expression profiles in neuronal stem cell, mitomycin-treated neuronal stem cells and primary neuronal cultures were compared to examine cellular morphology and gene expression signatures during neuronal differentiation.

ORGANISM(S): Mus musculus  

SUBMITTER: Jin Xue   Hady Felfly  Gabriel G Haddad  Dan Zhou 

PROVIDER: E-GEOD-24116 | ArrayExpress | 2011-11-28

SECONDARY ACCESSION(S): GSE24116PRJNA130049

REPOSITORIES: GEO, ArrayExpress

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Identification of a neuronal gene expression signature: role of cell cycle arrest in murine neuronal differentiation in vitro.

Felfly Hady H   Xue Jin J   Zambon Alexander C AC   Muotri Alysson A   Zhou Dan D   Haddad Gabriel G GG  

American journal of physiology. Regulatory, integrative and comparative physiology 20110615 3


Stem cells are a potential key strategy for treating neurodegenerative diseases in which the generation of new neurons is critical. A better understanding of the characteristics and molecular properties of neural stem cells (NSCs) and differentiated neurons can help with assessing neuronal maturity and, possibly, in devising better therapeutic strategies. We have performed an in-depth gene expression profiling study of murine NSCs and primary neurons derived from embryonic mouse brains. Microarr  ...[more]

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