System approaches reveal the molecular networks involved in neural stem cell differentiation

Kai Wang1,5, Haifeng Wang2,5, Jiao Wang2,5, Yuqiong Xie1,5, Jun Chen3,4, Huang Yan1,5, Zengrong Liu5, Tieqiao Wen1,5()

PDF(740 KB)
PDF(740 KB)
Protein Cell ›› 2012, Vol. 3 ›› Issue (3) : 213-224. DOI: 10.1007/s13238-012-0014-4
RESEARCH ARTICLE

System approaches reveal the molecular networks involved in neural stem cell differentiation

  • Kai Wang1,5, Haifeng Wang2,5, Jiao Wang2,5, Yuqiong Xie1,5, Jun Chen3,4, Huang Yan1,5, Zengrong Liu5, Tieqiao Wen1,5()
Author information +
History +

Abstract

The self-renewal and multipotent potentials in neural stem cells (NSCs) maintain the normal physiological functions of central nervous system (CNS). The abnormal differentiation of NSCs would lead to CNS disorders. However, the mechanisms of how NSCs differentiate into astrocytes, oligodendrocytes (OLs) and neurons are still unclear, which is mainly due to the complexity of differentiation processes and the limitation of the cell separation method. In this study, we modeled the dynamics of neural cell interactions in a systemic approach by mining the high-throughput genomic and proteomic data, and identified 8615 genes that are involved in various biological processes and functions with significant changes during the differentiation processes. A total of 1559 genes are specifically expressed in neural cells, in which 242 genes are NSC specific, 215 are astrocyte specific, 551 are OL specific, and 563 are neuron specific. In addition, we proposed 57 transcriptional regulators specifically expressed in NSCs may play essential roles in the development courses. These findings provide more comprehensive analysis for better understanding the endogenous mechanisms of NSC fate determination.

Keywords

neural stem cell / cell differentiation / molecular networks

Cite this article

Download citation ▾
Kai Wang, Haifeng Wang, Jiao Wang, Yuqiong Xie, Jun Chen, Huang Yan, Zengrong Liu, Tieqiao Wen. System approaches reveal the molecular networks involved in neural stem cell differentiation. Prot Cell, 2012, 3(3): 213‒224 https://doi.org/10.1007/s13238-012-0014-4

References

[1] Andersson, T., Sodersten, E., Duckworth, J.K., Cascante, A., Fritz, N., Sacchetti, P., Cervenka, I., Bryja, V., and Hermanson, O. (2009). CXXC5 is a novel BMP4-regulated modulator of Wnt signaling in neural stem cells. J Biol Chem 284, 3672-3681 .10.1074/jbc.M808119200
[2] Aranda, B., Achuthan, P., Alam-Faruque, Y., Armean, I., Bridge, A., Derow, C., Feuermann, M., Ghanbarian, A.T., Kerrien, S., Khadake, J., . (2010). The IntAct molecular interaction database in 2010. Nucleic Acids Res 38, D525-531 .10.1093/nar/gkp878
[3] Barrett, T., Troup, D.B., Wilhite, S.E., Ledoux, P., Evangelista, C., Kim, I.F., Tomashevsky, M., Marshall, K.A., Phillippy, K.H., Sherman, P.M., . (2011). NCBI GEO: archive for functional genomics data sets—10 years on. Nucleic Acids Res 39, D1005-1010 .10.1093/nar/gkq1184
[4] Cahoy, J.D., Emery, B., Kaushal, A., Foo, L.C., Zamanian, J.L., Christopherson, K.S., Xing, Y., Lubischer, J.L., Krieg, P.A., Krupenko, S.A., . (2008). A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J Neurosci 28, 264-278 .10.1523/JNEUROSCI.4178-07.2008
[5] Chang, C.-C., and Lin, C.-J. (2011). LIBSVM: A library for support vector machines. ACM Trans Intell Syst Technol 2, 1-27 .
[6] Ding, C., and Peng, H. (2005). Minimum redundancy feature selection from microarray gene expression data. J Bioinform Comput Biol 3, 185-205 .10.1142/S0219720005001004
[7] Episkopou, V. (2005). SOX2 functions in adult neural stem cells. Trends Neurosci 28, 219-221 .10.1016/j.tins.2005.03.003
[8] Favaro, R., Valotta, M., Ferri, A.L., Latorre, E., Mariani, J., Giachino, C., Lancini, C., Tosetti, V., Ottolenghi, S., Taylor, V., . (2009). Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh. Nat Neurosci 12, 1248-1256 .10.1038/nn.2397
[9] Huang da, W., Sherman, B.T., and Lempicki, R.A. (2009a). Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37, 1-13 .10.1093/nar/gkn923
[10] Huang da, W., Sherman, B.T., and Lempicki, R.A. (2009b). Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4, 44-57 .
[11] Juliandi, B., Abematsu, M., and Nakashima, K. (2010). Epigenetic regulation in neural stem cell differentiation. Dev Growth Differ 52, 493-504 .10.1111/j.1440-169X.2010.01175.x
[12] Kim, J.B., Sebastiano, V., Wu, G., Arauzo-Bravo, M.J., Sasse, P., Gentile, L., Ko, K., Ruau, D., Ehrich, M., van den Boom, D., . (2009). Oct4-induced pluripotency in adult neural stem cells. Cell 136, 411-419 .10.1016/j.cell.2009.01.023
[13] Kimura, I., Nakayama, Y., Konishi, M., Kobayashi, T., Mori, M., Ito, M., Hirasawa, A., Tsujimoto, G., Ohta, M., Itoh, N., . (2010). Neuferricin, a novel extracellular heme-binding protein, promotes neurogenesis. J Neurochem 112, 1156-1167 .10.1111/j.1471-4159.2009.06522.x
[14] Kozomara, A., and Griffiths-Jones, S. (2011). miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 39, D152-157 .10.1093/nar/gkq1027
[15] Lee, S.T., Chu, K., Park, J.E., Lee, K., Kang, L., Kim, S.U., and Kim, M. (2005). Intravenous administration of human neural stem cells induces functional recovery in Huntington's disease rat model. Neurosci Res 52, 243-249 .10.1016/j.neures.2005.03.016
[16] Lessard, J., Wu, J.I., Ranish, J.A., Wan, M., Winslow, M.M., Staahl, B.T., Wu, H., Aebersold, R., Graef, I.A., and Crabtree, G.R. (2007). An essential switch in subunit composition of a chromatin remodeling complex during neural development. Neuron 55, 201-215 .10.1016/j.neuron.2007.06.019
[17] Maka, M., Stolt, C.C., and Wegner, M. (2005). Identification of Sox8 as a modifier gene in a mouse model of Hirschsprung disease reveals underlying molecular defect. Dev Biol 277, 155-169 .10.1016/j.ydbio.2004.09.014
[18] Makri, G., Lavdas, A.A., Katsimpardi, L., Charneau, P., Thomaidou, D., and Matsas, R. (2010). Transplantation of embryonic neural stem/precursor cells overexpressing BM88/Cend1 enhances the generation of neuronal cells in the injured mouse cortex. Stem Cells 28, 127-139 .
[19] Matsumoto, Y., and Osumi, N. (2008). [Role of Pax6 in the developing central nervous system]. Brain Nerve 60, 365-374 .
[20] Moghadam, F.H., Alaie, H., Karbalaie, K., Tanhaei, S., Nasr Esfahani, M.H., and Baharvand, H. (2009). Transplantation of primed or unprimed mouse embryonic stem cell-derived neural precursor cells improves cognitive function in Alzheimerian rats. Differentiation 78, 59-68 .10.1016/j.diff.2009.06.005
[21] Namihira, M., Kohyama, J., Abematsu, M., and Nakashima, K. (2008). Epigenetic mechanisms regulating fate specification of neural stem cells. Philos Trans R Soc Lond B Biol Sci 363, 2099-2109 .10.1098/rstb.2008.2262
[22] Oliveira, A.A., Jr., and Hodges, H.M. (2005). Alzheimer's disease and neural transplantation as prospective cell therapy. Curr Alzheimer Res 2, 79-95 .10.2174/1567205052772759
[23] Osumi, N., Shinohara, H., Numayama-Tsuruta, K., and Maekawa, M. (2008). Concise review: Pax6 transcription factor contributes to both embryonic and adult neurogenesis as a multifunctional regulator. Stem Cells 26, 1663-1672 .10.1634/stemcells.2007-0884
[24] Park, D., Xiang, A.P., Mao, F.F., Zhang, L., Di, C.G., Liu, X.M., Shao, Y., Ma, B.F., Lee, J.H., Ha, K.S., . (2010). Nestin is required for the proper self-renewal of neural stem cells. Stem Cells 28, 2162-2171 .10.1002/stem.541
[25] Park, J.H., Choi, M.R., Park, K.S., Kim, S.H., Jung, K.H., and Chai, Y.G. (2012). The characterization of gene expression during mouse neural stem cell differentiation in vitro. Neurosci Lett 506, 50-54 .10.1016/j.neulet.2011.10.046
[26] Peng, H., Long, F., and Ding, C. (2005). Feature selection based on mutual information: criteria of max-dependency, max-relevance, and min-redundancy. IEEE Trans Pattern Anal Mach Intell 27, 1226-1238 .10.1109/TPAMI.2005.159
[27] Peng, H., Long, F., Zhou, J., Leung, G., Eisen, M.B., and Myers, E.W. (2007). Automatic image analysis for gene expression patterns of fly embryos. BMC Cell Biol 8 Suppl 1, S7.10.1186/1471-2121-8-S1-S7
[28] Portales-Casamar, E., Thongjuea, S., Kwon, A.T., Arenillas, D., Zhao, X., Valen, E., Yusuf, D., Lenhard, B., Wasserman, W.W., and Sandelin, A. (2010). JASPAR 2010: the greatly expanded open-access database of transcription factor binding profiles. Nucleic Acids Res 38, D105-110 .10.1093/nar/gkp950
[29] Renault, V.M., Rafalski, V.A., Morgan, A.A., Salih, D.A., Brett, J.O., Webb, A.E., Villeda, S.A., Thekkat, P.U., Guillerey, C., Denko, N.C., . (2009). FoxO3 regulates neural stem cell homeostasis. Cell Stem Cell 5, 527-539 .10.1016/j.stem.2009.09.014
[30] Salwinski, L., Miller, C.S., Smith, A.J., Pettit, F.K., Bowie, J.U., and Eisenberg, D. (2004). The Database of Interacting Proteins: 2004 update. Nucleic Acids Res 32, D449-451 .10.1093/nar/gkh086
[31] Sanberg, P.R. (2007). Neural stem cells for Parkinson's disease: to protect and repair. Proc Natl Acad Sci U S A 104, 11869-11870 .10.1073/pnas.0704704104
[32] Stark, C., Breitkreutz, B.J., Chatr-Aryamontri, A., Boucher, L., Oughtred, R., Livstone, M.S., Nixon, J., Van Auken, K., Wang, X., Shi, X., . (2011). The BioGRID Interaction Database: 2011 update. Nucleic Acids Res 39, D698-704 .10.1093/nar/gkq1116
[33] Steffen, M., Petti, A., Aach, J., D'Haeseleer, P., and Church, G. (2002). Automated modelling of signal transduction networks. BMC Bioinformatics 3, 34.10.1186/1471-2105-3-34
[34] Storch, A., and Schwarz, J. (2002). Neural stem cells and Parkinson's disease. J Neurol 249Suppl 3, III/30-32 .
[35] Suzuki, H., Forrest, A.R., van Nimwegen, E., Daub, C.O., Balwierz, P.J., Irvine, K.M., Lassmann, T., Ravasi, T., Hasegawa, Y., de Hoon, M.J., . (2009). The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line. Nat Genet 41, 553-562 .10.1038/ng.375
[36] Szklarczyk, D., Franceschini, A., Kuhn, M., Simonovic, M., Roth, A., Minguez, P., Doerks, T., Stark, M., Muller, J., Bork, P., . (2011). The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res 39, D561-568 .10.1093/nar/gkq973
[37] Tang, J., Xu, H., Fan, X., Li, D., Rancourt, D., Zhou, G., Li, Z., and Yang, L. (2008). Embryonic stem cell-derived neural precursor cells improve memory dysfunction in Abeta(1-40) injured rats. Neurosci Res 62, 86-96 .10.1016/j.neures.2008.06.005
[38] Temple, S. (2001). The development of neural stem cells. Nature 414, 112-117 .10.1038/35102174
[39] Thorrez, L., Van Deun, K., Tranchevent, L.C., Van Lommel, L., Engelen, K., Marchal, K., Moreau, Y., Van Mechelen, I., and Schuit, F. (2008). Using ribosomal protein genes as reference: a tale of caution. PLoS One 3, e1854.
[40] Ueki, T., Tanaka, M., Yamashita, K., Mikawa, S., Qiu, Z., Maragakis, N.J., Hevner, R.F., Miura, N., Sugimura, H., and Sato, K. (2003). A novel secretory factor, Neurogenesin-1, provides neurogenic environmental cues for neural stem cells in the adult hippocampus. J Neurosci 23, 11732-11740 .
[41] Wang, K., Hu, F., Xu, K., Cheng, H., Jiang, M., Feng, R., Li, J., and Wen, T. (2011). CASCADE_SCAN: mining signal transduction network from high-throughput data based on steepest descent method. BMC Bioinformatics 12, 164.10.1186/1471-2105-12-164
[42] Wang, K., Hu, L., Shi, X., Dong, Y., Li, H., and Wen, T. (2012). PSCL: Predicting protein subcellular localization based on optimal functional domains. Protein Pept Lett 19, 15-22 .
[43] Wu, Z., Irizarry, R., Gentleman, R., Martinez-Murillo, F., and Spencer, F. (2004). A model-based background adjustment for oligonucleotide expression arrays. J Am Stat Assoc . 99, 909-917 .10.1198/016214504000000683
[44] Zhao, X.M., Wang, R.S., Chen, L., and Aihara, K. (2008). Uncovering signal transduction networks from high-throughput data by integer linear programming. Nucleic Acids Res 36, e48.10.1093/nar/gkn145
[45] Zhongling, F., Gang, Z., and Lei, Y. (2009). Neural stem cells and Alzheimer's disease: challenges and hope. Am J Alzheimers Dis Other Demen 24, 52-57 .10.1177/1533317508327587
AI Summary AI Mindmap
PDF(740 KB)

Accesses

Citations

Detail

Sections
Recommended

/