High-throughput screening using iPSC-derived neuronal progenitors to identify compounds counteracting epigenetic gene silencing in fragile X syndrome

Journal of Biomolecular Screening

Volumn 20, Issue 9, 2015, Pages 1101-1111

  Kaufmann, Markus ^a   Schuffenhauer, Ansgar ^a   Fruh, Isabelle ^a   Klein, Jessica ^a   Thiemeyer, Anke ^a   Rigo, Pierre ^a   Gomez Mancilla, Baltazar ^a   Heidinger Millot, Valerie ^a   Bouwmeester, Tewis ^a   Schopfer, Ulrich ^a   Mueller, Matthias ^a   Fodor, Barna D ^a   Cobos Correa, Amanda ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

fragile X syndrome; high content screening; induced pluripotent stem cells

Indexed keywords

DECITABINE; DNA METHYLTRANSFERASE 1; FRAGILE X MENTAL RETARDATION PROTEIN; FMR1 PROTEIN, HUMAN;

ARTICLE; BIODIVERSITY; CELL ADHESION; CELL DENSITY; CELL POPULATION; CELLULAR DISTRIBUTION; CONTROLLED STUDY; CYTOPLASM; DISEASE MODEL; DNA REPLICATION; DRUG SCREENING; EC50; EPIGENETICS; FIBROBLAST; FLUORESCENCE ACTIVATED CELL SORTING; FRAGILE X SYNDROME; GENE SILENCING; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; HUMAN TISSUE; HYBRIDIZATION; IMAGE ANALYSIS; LYMPHOBLASTOID CELL; NEURAL STEM CELL; NEWBORN; PHENOTYPE; PLEIOTROPY; PLURIPOTENT STEM CELL; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PYROSEQUENCING; RANDOM FOREST; SCALE UP; SINGLE CELL ANALYSIS; SOUTHERN BLOTTING; CELL CULTURE; DRUG EFFECTS; GENETICS; INDUCED PLURIPOTENT STEM CELL; METABOLISM; PHYSIOLOGY; PRECLINICAL STUDY; TRINUCLEOTIDE REPEAT;

CELLS, CULTURED; DRUG EVALUATION, PRECLINICAL; FRAGILE X MENTAL RETARDATION PROTEIN; FRAGILE X SYNDROME; GENE SILENCING; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; INDUCED PLURIPOTENT STEM CELLS; NEURAL STEM CELLS; TRINUCLEOTIDE REPEATS;

EID: 84942114523     PISSN: 10870571     EISSN: 1552454X     Source Type: Journal    
DOI: 10.1177/1087057115588287     Document Type: Article

References (30)

1. Bagni C., Tassone F., Neri G., et al. Fragile X Syndrome: Causes, Diagnosis, Mechanisms, and Therapeutics. J. Clin. Invest. 2012, 122, 4314-4322.
2. Sidorov M., Auerbach B., Bear M., Fragile X Mental Retardation Protein and Synaptic Plasticity. Mol. Brain 2013, 6, 15.
3. Tassone F., Hagerman R. J., Iklé D. N., et al. FMRP Expression as a Potential Prognostic Indicator in Fragile X Syndrome. Am. J. Med. Genet. 1999, 84, 250-261.
4. Smeets H. J. M., Smits A. P. T., Verheij C. E., et al. Normal Phenotype in Two Brothers with a Full Fmr1 Mutation. Hum. Mol. Genet. 1995, 4, 2103-2108.
5. Jacquemont S., Curie A., des Portes V., et al. Epigenetic Modification of the Fmr1 Gene in Fragile X Syndrome Is Associated with Differential Response to the mGluR5 Antagonist AFQ056. Sci. Transl. Med. 2011, 3, 64ra1.
6. Bakker C. E., Verheij C., Willemsen R., et al. Fmr1 Knockout Mice: A Model to Study Fragile X Mental Retardation. Cell 1994, 78, 23-33.
7. Comery T. A., Harris J. B., Willems P. J., et al. Abnormal Dendritic Spines in Fragile X Knockout Mice: Maturation and Pruning-Deficits. Proc. Natl. Acad. Sci. U. S. A. 1997, 94, 5401-5404.
8. Spencer C. M., Graham D. F., Yuva-Paylor L. A., et al. Social Behavior in Fmr1 Knockout Mice Carrying a Human Fmr1 Transgene. Behav. Neurosci. 2008, 122, 710-715.
9. Berman R., Buijsen R., Usdin K., et al. Mouse Models of the Fragile X Premutation and Fragile X-Associated Tremor/Ataxia Syndrome. J. Neurodev. Disord. 2014, 6, 25.
10. Bontekoe C. J. M., Bakker C. E., Nieuwenhuizen I. M., et al. Instability of a (CGG)98 Repeat in the Fmr1 Promoter. Hum. Mol. Genet. 2001, 10, 1693-1699.
11. Grskovic M., Javaherian A., Strulovici B., et al. Induced Pluripotent Stem Cells-Opportunities for Disease Modelling and Drug Discovery. Nat. Rev. Drug Discov. 2011, 10, 915-929.
12. Xu X.-H., Zhong Z., Disease Modeling and Drug Screening for Neurological Diseases Using Human Induced Pluripotent Stem Cells. Acta Pharmacol. Sin. 2013, 34, 755-764.
13. Sandoe J., Eggan K., Opportunities and Challenges of Pluripotent Stem Cell Neurodegenerative Disease Models. Nat. Neurosci. 2013, 16, 780-789.
14. Urbach A., Bar-Nur O., Daley G., et al. Differential Modelling of Fragile X Syndrome by Human Embryonic Stem Cells and Induced Pluripotent Stem Cells. Cell Stem Cell 2010, 6, 407-411.
15. Bar-Nur O., Caspi I., Benvenisty N., Molecular Analysis of Fmr1 Reactivation in Fragile-X Induced Pluripotent Stem Cells and Their Neuronal Derivatives. J. Mol. Cell Biol. 2012, 4, 180-183.
16. Garber K., Between Disease and a Dish. Nat. Biotechnol. 2014, 32, 712-715.
17. Hagerman R., Des Portes V., Gasparini F., et al. Translating Molecular Advances in Fragile X Syndrome into Therapy. J. Clin. Psychiatry 2014, 75, e294-e307.
18. Liu J., Kos̈cielska K. A., Cao Z., et al. Signaling Defects in iPSC-Derived Fragile X Premutation Neurons. Hum. Mol. Genet. 2012, 21, 3795-3805.
19. Colak D., Zaninovic N., Cohen MS., et al. Promoter-Bound Trinucleotide Repeat mRNA Drives Epigenetic Silencing in Fragile X Syndrome. Science 2014, 343, 1002-1005.
20. Park I.-H., Lerou P., Zhao R., et al. Generation of Human-Induced Pluripotent Stem Cells. Nat. Protocols 2008, 3, 1180-1186.
21. Chambers S. M., Fasano C.A., Papapetrou E.P., et al. Highly Efficient Neural Conversion of Human ES and iPS Cells by Dual Inhibition of SMAD Signaling. Nat. Biotechnol. 2009, 27, 275-280.
22. Pecho-Vrieseling E., Rieker C., Fuchs S., et al. Transneuronal Propagation of Mutant huntingtin Contributes to Non-Cell Autonomous Pathology in Neurons. Nat. Neurosci. 2014, 17, 1064-1072.
23. Oberle I., Rousseau F., Heitz D., et al. Instability of a 550-Base Pair DNA Segment and Abnormal Methylation in Fragile X Syndrome. Science 1991, 252, 1097-1102.
24. Filipovic-Sadic S., Sah S., Chen L., et al. A Novel Fmr1 PCR Method for the Routine Detection of Low Abundance Expanded Alleles and Full Mutations in Fragile X Syndrome. Clin. Chem. 2010, 56, 399-408.
25. Gubler H., Methods for Statistical Analysis, Quality Assurance and Management of Primary High-Throughput Screening Data. In High-Throughput Screening in Drug Discovery; Hüser J., Ed.; Wiley-VCH Verlag GmbH & Co. KGaA: New York, 2006, pp. 151-205.
26. Chiurazzi P., Grazia Pomponi M., Pietrobono R., et al. Synergistic Effect of Histone Hyperacetylation and DNA Demethylation in the Reactivation of the Fmr1 Gene. Hum. Mol. Genet. 1999, 8, 2317-2323.
27. Yuan S. H., Martin J., Elia J., et al. Cell-Surface Marker Signatures for the Isolation of Neural Stem Cells, Glia and Neurons Derived from Human Pluripotent Stem Cells. PLoS ONE 2011, 6, e17540.
28. Sigalotti L., Fratta E., Coral S., et al. Epigenetic Drugs as Pleiotropic Agents in Cancer Treatment: Biomolecular Aspects and Clinical Applications. J. Cell. Physiol. 2007, 212, 330-344.
29. Schulz M., et al. Hydroxamate-based inhibitors of deacetylases B., Patent WO 2009118305 A1., 2009.
30. Kazantsev A. G., Thompson L. M., Therapeutic Application of Histone Deacetylase Inhibitors for Central Nervous System Disorders. Nat. Rev. Drug Discov. 2008, 7, 854-868.