Research of molecular markers and regulatory mechanism in neural stem cells

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Ουρίας Αλεξάκης
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1 Chinese Bulletin of Life Sciences Vol. 17, No.3 Jun., (2005) (NSC) (component plane presentation integrated self-organizing map, CPP-SOM) Q24; TP391.7 A Research of molecular markers and regulatory mechanism in neural stem cells CHEN Rui 1,2, LIU Di 2, ZHANG Ji 1 * (1Shanghai Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai , China; 2College of Animal Science and Technology, Northeast Agriculture University, Harbin , China) Abstract: Neural stem cells have received great attention not only for their roles in normal development but also for their potential use in the neurodegenerative disorders. Factors that control the proliferation and differentiation of NSCs have been identified in vitro. But lacking of specific markers results in few understandings of NSCs in vivo. The application of microarray make it possible to obtain the markers of NSCs in vivo. Furthermore through an effective data analysis method (CPP-SOM ), the study of gene expression and molecular regulatory in NSCs is achieved more deeply. Key words: neural stem cells microarray specific markers regulatory mechanism (pluripotent cells) (ES) [1~2] (1) (CNS) (PNS); (2) (3) (progenitor) [3~4] No (1979 ) (1963 ) (1938 ) *

2 257 (neurosphere) [5] (multipotent) (subventricular zone SVZ) (subgranular zone SGZ) (OE) (CMZ) 1.2 NSC CNS NSC NSC [6] NSC NSC [4] NSC NSC [7] NSC (asymmetric cell division) progenitor [8] Numb Notch Numb Numb Numb [9] NSC [10] NSC (FGF) NSC (EGF) EGF NSC -β (TGF-β) (BMP) (BMP) [11] (CNTF) NSC BMP CNTF [12] BMP CNTF NSC Notch Wnt Sonic Hedgehog (Shh) Notch

3 258 Notch Notch [13] Wnt Wnt-1 Wnt-3a p19 [14] Wnt Shh NSC cyclinds mrna G 1 [15] NSC NSC NSC NSC CMZ cyclina2 cycline1 cyclind1 cdc cdk2 p27 Kip1 NSC Sox2 Sox2 [16] NSC NSC [17] NSC NSC [18] progenitor NSC [19] NSC Nestin [20] (NEP) Nestin Nestin Notch Numb Presenilin (FACS) Uchida [7] CD133 NEP Nestin

4 259 (GFP) EGFP + RC2 NSC [21] E10.5 NEP NSC (E-NCAM) [22] NSC NSC cdna NSC [23] Luo [18] cdna NSC NSC Tubb3 Cdkn1b Nf1 NSC 2.2 NSC Geschwind [19] cdna E13d NSC NSC progenitor Geschwind (HSC) NSC CyclinD1 (ERCC1) Ivanova [24] Affymetrix ES HSC NSC 283 NSC ES 783 HSC 644 NSC Karsten [25] NSC Gene Ontology 12 NSC Cyclin B, D1, D2 Cdc28 G 1 S p18 p21 DNA NSC NSC NSC Ramalho- Santos [26] (1) JAK-STAT TGF-β Nothch YES (2) (3) (4) DNA (5) (6)RNA

5 260 CPP-SOM(component plane presentation integrated self-organizing map) [27] SOM NSC NSC NSC NSC [1] Odorico J S, Kaufman D S, Thomson J A. Multilineage differentiation from human embryonic stem cell lines. Stem Cells, 2001, 19: 193~204 [2] Donovan P J, Gearhart J. The end of the beginning for pluripotent stem cells. Nature, 2001, 414: 92~97 [3] Temple S. Division and differentiation of isolated CNS blast cells in microculture. Nature, 1989, 340: 471~473 [4] Temple S. Defining neural stem cells and their role in normal development of the nervous system[a]. In: Mashendra S Rao, ed.stem cell and CNS development[c]. Salt Lake City, UT: Humana Press, 2001, 1~29 [5] Anderson D J, Groves A, Lo l, et al. Cell lineage determination and the control of neuronal identity in the neural crest. Cold Spring Harb Symp Quant Biol, 1997, 62: 493~504 [6] Tropepe V, Hitoshi S, Ekker M, et al. Neural stem cells and their progeny express region-specific gene in the developing CNS, but this expression is not irreversible and can be a-ltered by local inductive cues. Soc Neurosci, 2000, Abstr.23. [7] Uchida N, Buck D W, He D, et al. Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci USA, 2000, 97: 14720~14725 [8] Roegiers F, Jan Y N. Asymmetric cell division. Curr Opin Cell Biol, 2004, 16: 1~11 [9] Shen Q, Zhong W M, Jan Y N, et al. Asymmetric Numb distribution is critical for asymmetric cell division of mouse cerebral cortical stem cells and neuroblasts. Development, 2002, 129: 4843~4853 [10] Johe K K, Hazel T G, Muller T, et al. Single factors direct the differentiation of stem cells from the fetal and adult central nervous system. Genes Dev, 1996, 10: 3129~3140 [11] Temple S. The development of neural stem cells. Nature, 2001, 414: 112~117 [12] Gross R E, Mehler M F,Mabie P C, et al. Bone morphogenetic proteins promote astroglial lineage commitment by mammalian subventricular zone progenitor cells. Neuron, 1996, 17: 595~606 [13] Kessler J A, Mehler M F, Mabie P. Multipotent Stem cells in the embryonic nervous system[a]. In: Mahendra S.Rao. Stem Cells and CNS Development[C]. Salt Lakl City, UT: Human Press, 2001, 31~48 [14] Muroyama Y, Kondoh H, Takada S. Wnt proteins promote neuronal differentiation in neural stem cell culture. Biochem Biophys Res Commun, 2004, 313: 915~921 [15] Kenney A M, Rowitch D H. Sonic hedgehog promotes G 1 cyclin expression and sustained cell cycle progression in mammalian neuronal precursors. Mol Cell Biol, 2000, 20: 9055~9067 [16] Ohnuma S I, Harris W A. Neurogenesis and the cell cycle. Neuron, 2003, 40: 199~208 [17] Martinez-Serrano A, Björklund A. Protection of the neostriatum against excitotoxic damage by neurotrophinproducing, genetically modified neural stem cells. J Neurosci, 1996, 16: 4604~4616 [18] Luo Y Q, Cai J L, Ginis I, et al. Designing, testing, and validating a focused stem cell microarray for characterization of neural stem cells and progenitor cells. Stem Cells, 2003, 21: 575~587 [19] Geschwind D H, Ou J, Easterday M C, et al. A genetic analysis of neural progenitor differenti-ation. Neuron, 2001, 29: 325~339 [20] Frederiksen K, Mckay R D. Proliferation and differentiation of rat neuroepithelial precursor cells in vivo. J Neurosci, 1988, 8: 1144~1151 [21] Kawaguchi A, Miyata T, Sawamoto K, et al. Nestin-EGFP transgenic mice:visualization of the se-lfrenewal and multipotency of CNS stem cells. Mol Cell Neurosci, 2001, 17: 259~273 [22] Cai J L, Wu Y Y, Mirua T, et al. Properties of a fetal multipotent neural stem cell (NEP Cell). Dev Biol, 2002, 251: 221~240 [23] Kornblum H I, Geschwind D H. Molecular markers in CNS stem cell research: hitting a moving target. Nat Rev Neurosci, 2001, 2: 843~846 [24] Ivanova N B, Dimos J T, Schaniel C, et al. A stem cell molecular signature. Science, 2002, 298: 601~604 [25] Karsten S L, Kudo L C, Jackson R, et al. Global analysis of gene expression in neural progenitors reveals specific cellcycle, signaling, and metabolic networks. Dev Biol, 2003, 261: 165~182 [26] Ramalho-Santos M, Yoon S, Matsuzaki Y, et al. Stemness : transcriptional profiling of embryonic and adult stem cells. Science, 2002, 298: 597~600 [27] Xiao L, Wang K K, Teng Y, et al. Component plane presentation integrated self-organizing map for microarray data analysis. FEBS Lett, 2003, 538: 117~224

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