Abstract
Pluripotent stem cell lines derived from donors who carry a mutant gene at the origin of a monogenic disease can be obtained currently either from embryos that are characterized as gene carriers during a pre-implantation genetic diagnosis (PGD) procedure or through genetic reprogramming of donors’ sample cells. Both methods can be used to screen libraries of compounds in a search for new treatments. Currently, the embryonic stem (ES) cell bank at I-Stem comprises over 30 PGD-derived cell lines representing over 15 diseases. Induced pluripotent stem (iPS) cell lines are derived upon request and I-Stem welcomes colleagues who need iPS cell lines in its “iPS workshop” (see www.istem.eu). Robust read-outs relevant to the pathological mechanisms should first be identified. On this basis, a screening platform either in high throughput or in high content can be implemented, as derivatives of pluripotent stem cells can be obtained at near homogeneity and are amenable to miniaturization and standardization of cell processes. At I-Stem, we have already exploited this potential for several pathologies that affect the brain, including Huntington’s disease, Myotonic Dystrophy type I and Lesch-Nyhan disease. In parallel, functional genomics can also be implemented on large-scale platforms, in a search for yet unknown mechanisms and proteins involved in pathological signaling pathways.
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Agarwal S, Loh YH, McLoughlin EM, Huang J, Park IH, Miller JD, Huo H, Okuka M, Dos Reis RM, Loewer S, Ng HH, Keefe DL, Goldman FD, Klingelhutz AJ, Liu L, Daley Q (2010) Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients. Nature 464:292–296
Anderson SL, Coli R, Daly IW, Kichula EA, Rork MJ, Volpi SA, Ekstein J, Rubin BY (2001) Familial dysautonomia is caused by mutations of the IKAP gene. Am J Hum Genet 68:753–758
Brennand KJ, Simone A, Jou J, Gelboin-Burkhart C, Tran N, Sangar S, Li Y, Mu Y, Chen G, Yu D, McCarthy S, Sebat J, Gage FH (2011) Modelling schizophrenia using human induced pluripotent stem cells. Nature 473:221–225
Chang T, Zheng W, Tsark W, Bates S, Huang H, Lin RJ, Yee JK (2011) Phenotypic rescue of induced pluripotent stem cell-derived motoneurons of a spinal muscular atrophy patient. Stem Cells 29(12):2090–2093
Desbordes SC, Placantonakis DG, Ciro A, Ciro A, Socci ND, Lee G, Djaballah H, Studer L (2008) High-throughput screening assay for the identification of compounds regulating self-renewal and differentiation in human embryonic stem cells. Cell Stem Cell 2:602–612
Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM, Mitsumoto H, Chung W, Croft GF, Saphier G, Leibel R, Goland R, Wichterle H, Henderson CE, Eggan K (2008) Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321:1218–1221
Ebert AD, Yu J, Rose FF Jr, Mattis VB, Lorson CL, Thomson JA, Svendsen CN (2009) Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 457:277–280
Jiang H, Mankodi A, Swanson MS, Moxley RT, Thornton CA (2004) Myotonic dystrophy type 1 is associated with nuclear foci of mutant RNA, sequestration of muscleblind proteins and deregulated alternative splicing in neurons. Hum Mol Genet 13:3079–3088
Lee JE, Cooper TA (2009) Pathogenic mechanisms of myotonic dystrophy. Biochem Soc Trans 37(Pt 6):1281–1286
Lee G, Papapetrou EP, Kim H, Chambers SM, Tomishima MJ, Fasano CA, Ganat YM, Menon J, Shimizu F, Viale A, Tabar V, Sadelain M, Studer L (2009) Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature 461:402–406
Liu Y, Lacson R, Cassaday J, Ross DA, Kreamer A, Hudak E, Peltier R, McLaren D, Muñoz-Sanjuan I, Santini F, Strulovici B, Ferrer M (2009) Identification of small-molecule modulators of mouse SVZ progenitor cell proliferation and differentiation through high-throughput screening. J Biomol Screen 14:319–329
Marchetto MC, Carromeu C, Acab A, Yu D, Yeo GW, Mu Y, Chen G, Gage FH, Muotri AR (2010) A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell 143:527–539
Marteyn A, Maury Y, Gauthier MM, Lecuyer C, Vernet R, Denis JA, Pietu G, Peschanski M, Martinat C (2011) Mutant human embryonic stem cells reveal neurite and synapse formation defects in type 1 myotonic dystrophy. Cell Stem Cell 8:434–444
Park IH, Arora N, Huo H, Maherali N, Ahfeldt T, Shimamura A, Lensch MW, Cowan C, Hochedlinger K, Daley GQ (2008) Disease-specific induced pluripotent stem cells. Cell 134:877–886
Sareen D, Ebert AD, Heins BM, McGivern JV, Ornelas L, Svendsen CN (2012) Inhibition of apoptosis blocks human motor neuron cell death in a stem cell model of spinal muscular atrophy. PLoS One 7(6):e39113
Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872
Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147
Tolar J, Xia L, Riddle Mj MJ, Lees CJ, Eide CR, McElmurry RT, Titeux M, OsbornMJ LTC, Hovnanian A, Wagner JE, Blazar BR (2010) Induced pluripotent stem cells from individuals with recessive dystrophic epidermolysis bullosa. J Invest Dermatol 131:848–856
Urbach A, Schuldiner M, Benvenisty N (2004) Modeling for Lesch–Nyhan disease by gene targeting in human embryonic stem cells. Stem Cells 22:635–641
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Peschanski, M., Martinat, C. (2013). Using Pluripotent Stem Cells to Decipher Mechanisms and Identify Treatments for Diseases That Affect the Brain. In: Gage, F., Christen, Y. (eds) Programmed Cells from Basic Neuroscience to Therapy. Research and Perspectives in Neurosciences, vol 20. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-36648-2_9
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DOI: https://doi.org/10.1007/978-3-642-36648-2_9
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