Abstract
Nuclear reprogramming changes the cell fate and plays a vital role in obtaining pluripotent stem cells. It is difficult to explain clear molecular mechanism of nuclear reprogramming. Direct reprogramming of somatic cell types into desired cell types can be achieved by using specific genes and small molecules. Computational methods and molecular modeling may provide the insight to explain the landscape of the nuclear reprogramming and stem cell pluripotency. The structural and functional information of protein is required for annotation. In the absence of experimental structures, computational methods like homology modeling will be employed to decipher the protein structure and active sites. By fold identification and binding site-based ligand association, functional annotation will be carried out. Molecular docking and pharmacophore modeling are used to optimize the lead compounds or small molecules for direct conversion of somatic cell types and stem cells into specific cell types, which also help in identification of the better targets that aid in drug design process in cell-based therapy and tissue engineering.
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Abbreviations
- Germ line stem cells:
-
GSCs
- Glial cell line-derived neurotrophic factor:
-
GDNF
- Induced pluripotent stem cells:
-
(iPS) cells
- Multipotent germ line stem cells:
-
mGSs
- Spermatogonial stem cells:
-
SSCs
References
Andrusier N, Nussinov R, Wolfson HJ (2007) FireDock: fast interaction refinement in molecular docking. Proteins: Structure, Function, and Bioinformatics 69(1):139–159
Arnold K, Bordoli L, Kopp J, Schwede T (2006) The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics 22(2):195–201
Beck KD, Valverde J, Alexi T, Poulsen K, Moffat B, Vandlen RA, Rosenthal A, Hefti F (1995) Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain. Nature 373(6512):339
Bensadoun JC, Déglon N, Tseng JL, Ridet JL, Zurn AD, Aebischer P (2000) Lentiviral vectors as a gene delivery system in the mouse midbrain: cellular and behavioral improvements in a 6-OHDA model of Parkinson’s disease using GDNF. Exp Neurol 164(1):15–24
Bowenkamp KE, Hoffman AF, Gerhardt GA, Henry MA, Biddle PT, Hoffer BJ, Granholm AC (1995) Glial cell line-derived neurotrophic factor supports survival of injured midbrain dopaminergic neurons. J Comp Neurol 355(4):479–489
Cochrane GR, Galperin MY (2009) The 2010 nucleic acids research database issue and online database collection: a community of data resources. Nucleic Acids Res 38(suppl_1):D1–D4
de Rooij DG (2006) Rapid expansion of the spermatogonial stem cell tool box. Proc Natl Acad Sci 103(21):7939–7940
Duhovny D, Nussinov R, Wolfson HJ (2002) Efficient unbound docking of rigid molecules. In: InInternational workshop on algorithms in bioinformatics. Springer, Berlin, Heidelberg, pp 185–200
Gash DM, Zhang Z, Ovadia A, Cass WA, Yi A, Simmerman L, Russell D, Martin D, Lapchak PA, Collins F, Hoffer BJ (1996) Functional recovery in parkinsonian monkeys treated with GDNF. Nature 380(6571):252
Gasteiger E, Hoogland C, Gattiker A, Wilkins MR, Appel RD, Bairoch A (2005) Protein identification and analysis tools on the ExPASy server. In: The proteomics protocols handbook. Humana press, pp 571–607. New York, USA
Hamra FK, Chapman KM, Nguyen DM, Williams-Stephens AA, Hammer RE, Garbers DL (2005) Self renewal, expansion, and transfection of rat spermatogonial stem cells in culture. Proc Natl Acad Sci U S A 102(48):17430–17435
Hebert MA, Van Horne CG, Hoffer BJ, Gerhardt GA (1996) Functional effects of GDNF in normal rat striatum: presynaptic studies using in vivo electrochemistry and microdialysis. J Pharmacol Exp Ther 279(3):1181–1190
Hess RA, Cooke PS, Hofmann MC, Murphy KM (2006) Mechanistic insights into the regulation of the spermatogonial stem cell niche. Cell Cycle 5(11):1164–1170
Hoffer BJ, Hoffman A, Bowenkamp K, Huettl P, Hudson J, Martin D, Lin LF, Gerhardt GA (1994) Glial cell line-derived neurotrophic factor reverses toxin-induced injury to midbrain dopaminergic neurons in vivo. Neurosci Lett 182(1):107–111
Honaramooz A, Megee S, Zeng W, Destrempes MM, Overton SA, Luo J, Galantino-Homer H, Modelski M, Chen F, Blash S, Melican DT (2008) Adeno-associated virus (AAV)-mediated transduction of male germ line stem cells results in transgene transmission after germ cell transplantation. FASEB J 22(2):374–382
Hudson J, Granholm AC, Gerhardt GA, Henry MA, Hoffman A, Biddle P, Leela NS, Mackerlova L, Lile JD, Collins F, Hoffer BJ (1995) Glial cell line-derived neurotrophic factor augments midbrain dopaminergic circuits in vivo. Brain Res Bull 36(5):425–432
Jung YH, Gupta MK, Oh SH, Uhm SJ, Lee HT (2010) Glial cell line-derived neurotrophic factor alters the growth characteristics and genomic imprinting of mouse multipotent adult germline stem cells. Exp Cell Res 316(5):747–761
Kanatsu-Shinohara M, Inoue K, Lee J, Yoshimoto M, Ogonuki N, Miki H, Baba S, Kato T, Kazuki Y, Toyokuni S, Toyoshima M (2004) Generation of pluripotent stem cells from neonatal mouse testis. Cell 119(7):1001–1012
Kim S, Thiessen PA, Bolton EE, Chen J, Fu G, Gindulyte A, Han L, He J, He S, Shoemaker BA, Wang J (2015) PubChem substance and compound databases. Nucleic Acids Res 44(D1):D1202–D1213
Kordower JH, Emborg ME, Bloch J, Ma SY, Chu Y, Leventhal L, McBride J, Chen EY, Palfi S, Roitberg BZ, Brown WD (2000) Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson’s disease. Science 290(5492):767–773
Kubota H, Avarbock MR, Brinster RL (2004) Growth factors essential for self-renewal and expansion of mouse spermatogonial stem cells. Proc Natl Acad Sci U S A 101(47):16489–16494
Laskowski RA, Swindells MB (2011) LigPlot+: multiple ligand–protein interaction diagrams for drug discovery. J Chem Inf Model 51:2778
Laskowski RA, Watson JD, Thornton JM (2005) ProFunc: a server for predicting protein function from 3D structure. Nucleic Acids Res 33(suppl_2):W89–W93
Li W, Ding S (2010) Small molecules that modulate embryonic stem cell fate and somatic cell reprogramming. Trends Pharmacol Sci 31(1):36–45
Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F (1993) GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260(5111):1130–1132
Lovell SC, Davis IW, Arendall WB, De Bakker PI, Word JM, Prisant MG, Richardson JS, Richardson DC (2003) Structure validation by Cα geometry: ϕ, ψ and Cβ deviation. Proteins: Structure, Function, and Bioinformatics. 50(3):437–450
Mashiach E, Schneidman-Duhovny D, Andrusier N, Nussinov R, Wolfson HJ (2008) FireDock: a web server for fast interaction refinement in molecular docking. Nucleic Acids Res 36(suppl_2):W229–W232
Meng X, Lindahl M, Hyvönen ME, Parvinen M, de Rooij DG, Hess MW, Raatikainen-Ahokas A, Sainio K, Rauvala H, Lakso M, Pichel JG (2000) Regulation of cell fate decision of undifferentiated spermatogonia by GDNF. Science 287(5457):1489–1493
Sauer H, Rosenblad C, Björklund A (1995) Glial cell line-derived neurotrophic factor but not transforming growth factor beta 3 prevents delayed degeneration of nigral dopaminergic neurons following striatal 6-hydroxydopamine lesion. Proc Natl Acad Sci 92(19):8935–8939
Schneidman-Duhovny D, Inbar Y, Nussinov R, Wolfson HJ (2005) PatchDock and SymmDock: servers for rigid and symmetric docking. Nucleic Acids Res 33(suppl_2):W363–W367
Schnieke AE, Kind AJ, Ritchie WA, Mycock K, Scott AR, Ritchie M, Wilmut I, Colman A, Campbell KH (1997) Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts. Science 278(5346):2130–2133
Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676
Tokugawa K, Yamamoto K, Nishiguchi M, Sekine T, Sakai M, Ueki T, Chaki S, Okuyama S (2003) XIB4035, a novel nonpeptidyl small molecule agonist for GFRα-1. Neurochem Int 42(1):81–86
VLife MD (2008) 3.5 Molecular design suite. VLife Sciences Technologies, Pune
Wallace AC, Laskowski RA, Thornton JM (1995) LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng Des Sel 8(2):127–134
Yamanaka S, Blau HM (2010) Nuclear reprogramming to a pluripotent state by three approaches. Nature 465(7299):704
Zechner U, Nolte J, Wolf M, Shirneshan K, Hajj NE, Weise D, Kaltwasser B, Zovoilis A, Haaf T, Engel W (2009) Comparative methylation profiles and telomerase biology of mouse multipotent adult germline stem cells and embryonic stem cells. Mol Hum Reprod 15(6):345–353
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The authors are thankful to Bioinformatics Infrastructure facility at National Institute of Technology, Rourkela funded by DBT for providing the facilities to carry out the research.
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Guttula, P.K., Gupta, M.K. (2019). Design and Development of Small Molecules from Somatic, Stem Cell Reprogramming, and Therapy. In: Shaik, N., Hakeem, K., Banaganapalli, B., Elango, R. (eds) Essentials of Bioinformatics, Volume II. Springer, Cham. https://doi.org/10.1007/978-3-030-18375-2_10
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DOI: https://doi.org/10.1007/978-3-030-18375-2_10
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