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Global Transcriptome Profiling of Genes that Are Differentially Regulated During Differentiation of Mouse Embryonic Neural Stem Cells into Astrocytes

Abstract

Many genes are associated with the differentiation of neural stem cells (NSCs) into astrocytes, the most abundant and functionally diverse population of glial cells in the central nervous system, particularly in the brain. In the present study, we differentiated NSCs from the forebrain of embryonic day 14.5 mouse embryos into astrocytes over 1 and 7 days. We identified transcriptomes of NSCs and astrocytes using RNA sequencing and analyzed enriched gene networks, signal pathways, and ontology. To identify important regulators of differentiation, we performed gene clustering according to expression patterns and promoter CG types. Our data show that genes related to system development, including Fbln2, Bcan, Ncam1, Itih3, Tnr, and Vcan, regulate NSC differentiation through WNT/beta-catenin and epithelial to mesenchymal transition pathways. We identified many CG-rich promoter genes related to basic cellular maintenance such as transcription, translation, and structural components and CG-poor promoter genes that are highly associated with cell-type-specific functions or play important roles during development. Our study provides a foundation for further research on NSC differentiation and the future application of stem cells.

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Acknowledgment

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No.2011-0030049).

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Correspondence to Young Gyu Chai.

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Figure S1
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Signaling pathway genes that showed enriched expression during 7-day differentiation (A) Signaling pathways during 7-day differentiation (B) Map of top scoring signaling pathways during 7-day differentiation (C), (D) mRNA expression of genes related to the Tgf-b pathway (C) and growth factors (D) in NSCs, differentiated cells, and primary cultured astrocytes by qRT-PCR. * Significantly different from NSCs by one-way ANOVA with HSD test (*P < 0.05, n = 3). (GIF 23 kb)

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Han, D., Choi, M.R., Jung, K.H. et al. Global Transcriptome Profiling of Genes that Are Differentially Regulated During Differentiation of Mouse Embryonic Neural Stem Cells into Astrocytes. J Mol Neurosci 55, 109–125 (2015). https://doi.org/10.1007/s12031-014-0382-8

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Keywords

  • Neural stem cells
  • Astrocytes
  • Cell differentiation
  • TGF beta
  • WNTs