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Neurobiology meets genomic science: The promise of human-induced pluripotent stem cells

Published online by Cambridge University Press:  15 October 2012

Hanna E. Stevens ,
Jessica Mariani ,
Gianfilippo Coppola  and
Flora M. Vaccarino
Hanna E. Stevens
Affiliation:
Yale University School of Medicine
Jessica Mariani
Affiliation:
Yale University School of Medicine
Gianfilippo Coppola
Affiliation:
Yale University School of Medicine
Flora M. Vaccarino*
Affiliation:
Yale University School of Medicine
*
Address correspondence and reprint requests to: Flora M. Vaccarino, Child Study Center, PO Box 207900, 230 South Frontage Road, Yale University School of Medicine, New Haven, CT 06520–7900; E-mail: [email protected].
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Abstract

The recent introduction of the induced pluripotent stem cell technology has made possible the derivation of neuronal cells from somatic cells obtained from human individuals. This in turn has opened new areas of investigation that can potentially bridge the gap between neuroscience and psychopathology. For the first time we can study the cell biology and genetics of neurons derived from any individual. Furthermore, by recapitulating in vitro the developmental steps whereby stem cells give rise to neuronal cells, we can now hope to understand factors that control typical and atypical development. We can begin to explore how human genes and their variants are transcribed into messenger RNAs within developing neurons and how these gene transcripts control the biology of developing cells. Thus, human-induced pluripotent stem cells have the potential to uncover not only what aspects of development are uniquely human but also variations in the series of events necessary for normal human brain development that predispose to psychopathology.

Type
Articles
Information
Development and Psychopathology , Volume 24 , Issue 4: Contributions of the Genetic/Genomic Sciences to Developmental Psychopathology , November 2012 , pp. 1443 - 1451
Copyright
Copyright © Cambridge University Press 2012

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References

Aasen, T., Raya, A., Barrero, M. J., Garreta, E., Consiglio, A., Gonzalez, F., et al. (2008). Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nature Biotechnology, 26, 1276–1284.Google Scholar
Acampora, D., Mazan, S., Lallemand, Y., Avantaggiato, V., Maury, M., Simeone, A., et al. (1995). Forebrain and midbrain regions are deleted in Otx2−/− mutants due to a defective anterior neuroectoderm specification during gastrulation. Development, 121, 3279–3290.Google Scholar
Alvarez-Buylla, A., Herrera, D. G., & Wichterle, H. (2000). The subventricular zone: source of neuronal precursors for brain repair. Progress in Brain Research, 127, 1–11.CrossRefGoogle ScholarPubMed
Anstrom, J. A., Thore, C. R., Moody, D. M., Challa, V. R., Block, S. M., & Brown, W. R. (2005). Germinal matrix cells associate with veins and a glial scaffold in the human fetal brain. Brain Research. Developmental Brain Research, 160, 96–100.CrossRefGoogle Scholar
Ayoub, A. E., Oh, S., Xie, Y., Leng, J., Cotney, J., Dominguez, M. H., et al. (2011). Transcriptional programs in transient embryonic zones of the cerebral cortex defined by high-resolution mRNA sequencing. Proceedings of the National Academy of Sciences, 108, 14950–14955.CrossRefGoogle ScholarPubMed
Ben-David, E., & Shifman, S. (2012). Networks of neuronal genes affected by common and rare variants in autism spectrum disorders. PLoS Genetics, 8, e1002556.Google Scholar
Boddaert, N., Chabane, N., Gervais, H., Good, C. D., Bourgeois, M., Plumet, M. H., et al. (2004). Superior temporal sulcus anatomical abnormalities in childhood autism: A voxel-based morphometry MRI study. NeuroImage, 23, 364–369.Google Scholar
Brennand, K. J., Simone, A., Jou, J., Gelboin-Burkhart, C., Tran, N., Sangar, S., et al. (2011). Modelling schizophrenia using human induced pluripotent stem cells. Nature, 473(7346), 221–225.Google Scholar
Campbell, D. B., Li, C., Sutcliffe, J. S., Persico, A. M., & Levitt, P. (2008). Genetic evidence implicating multiple genes in the MET receptor tyrosine kinase pathway in autism spectrum disorder. Autism Research, 1, 159–168.CrossRefGoogle ScholarPubMed
Carper, R. A., & Courchesne, E. (2005). Localized enlargement of the frontal cortex in early autism. Biological Psychiatry, 57, 126–133.Google Scholar
Casanova, M. F., Buxhoeveden, D. P., Switala, A. E., & Roy, E. (2002). Minicolumnar pathology in autism. Neurology, 58, 428–432.CrossRefGoogle ScholarPubMed
Chawarska, K., Campbell, D., Chen, L., Shic, F., Klin, A., & Chang, J. (2011). Early generalized overgrowth in boys with autism. Archives of General Psychiatry, 68, 1021–1031.Google Scholar
Clowry, G., Molnar, Z., & Rakic, P. (2010). Renewed focus on the developing human neocortex. Journal of Anatomy, 217, 276–288.Google Scholar
Colantuoni, C., Lipska, B. K., Ye, T., Hyde, T. M., Tao, R., Leek, J. T., et al. (2011). Temporal dynamics and genetic control of transcription in the human prefrontal cortex. Nature, 478(7370), 519–523.CrossRefGoogle ScholarPubMed
Constantin, G., Marconi, S., Rossi, B., Angiari, S., Calderan, L., Anghileri, E., et al. (2009). Adipose-derived mesenchymal stem cells ameliorate chronic experimental autoimmune encephalomyelitis. Stem Cells, 27, 2624–2635.CrossRefGoogle ScholarPubMed
Courchesne, E., Carper, R., & Akshoomoff, N. (2003). Evidence of brain overgrowth in the first year of life in autism. Journal of the American Medical Association, 290, 337–344.CrossRefGoogle ScholarPubMed
Courchesne, E., Mouton, P. R., Calhoun, M. E., Semendeferi, K., Ahrens-Barbeau, C., Hallet, M. J., et al. (2011). Neuron number and size in prefrontal cortex of children with autism. Journal of the American Medical Association, 306, 2001–2010.CrossRefGoogle ScholarPubMed
Courchesne, E., Redcay, E., & Kennedy, D. P. (2004). The autistic brain: Birth through adulthood. Current Opinion in Neurology, 17, 489–496.CrossRefGoogle ScholarPubMed
D'Hulst, C., & Kooy, R. F. (2009). Fragile X syndrome: From molecular genetics to therapy. Journal of Medical Genetics, 46, 577–584.CrossRefGoogle ScholarPubMed
Davidovitch, M., Patterson, B., & Gartside, P. (1996). Head circumference measurements in children with autism. Journal of Child Neurology, 11, 389–393.CrossRefGoogle ScholarPubMed
Dehay, C., & Kennedy, H. (2007). Cell-cycle control and cortical development. Nature Reviews Neuroscience, 8, 438–450.CrossRefGoogle ScholarPubMed
Dezawa, M., Kanno, H., Hoshino, M., Cho, H., Matsumoto, N., Itokazu, Y., et al. (2004). Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation. Journal of Clinical Investigation, 113, 1701–1710.Google Scholar
Ehninger, D., & Silva, A. J. (2011). Rapamycin for treating tuberous sclerosis and autism spectrum disorders. Trends in Molecular Medicine, 17, 78–87.CrossRefGoogle ScholarPubMed
Eiraku, M., Watanabe, K., Matsuo-Takasaki, M., Kawada, M., Yonemura, S., Matsumura, M., et al. (2008). Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals. Cell Stem Cell, 3, 519–532.Google Scholar
Fricker-Gates, R. A., & Gates, M. A. (2010). Stem cell-derived dopamine neurons for brain repair in Parkinson's disease. Regenerative Medicine, 5, 267–278.Google Scholar
Fusaki, N., Ban, H., Nishiyama, A., Saeki, K., & Hasegawa, M. (2009). Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome. Proceedings of the Japan Academy–Series B: Physical & Biological Sciences, 85, 348–362.Google Scholar
Geschwind, D. H. (2011). Neurodevelopmental disorders: hope for a new beginning. Current Opinion in Neurology, 24, 95–97.Google Scholar
Gurdon, J. B. (1987). Embryonic induction: Molecular prospects. Development, 99, 285–306.CrossRefGoogle ScholarPubMed
Gurdon, J. B. (1988). The origin of cell-type differences in early embryos. Cell Differentiation & Development, 25(Suppl.), 1–6.Google Scholar
Hansen, D. V., Rubenstein, J. L., & Kriegstein, A. R. (2011). Deriving excitatory neurons of the neocortex from pluripotent stem cells. Neuron, 70, 645–660.Google Scholar
Hariri, A. R., & Weinberger, D. R. (2003). Imaging genomics. British Medical Bulletin, 65, 259–270.Google Scholar
Hazlett, H. C., Poe, M. D., Gerig, G., Smith, R. G., & Piven, J. (2006). Cortical gray and white brain tissue volume in adolescents and adults with autism. Biological Psychiatry, 59, 1–6.Google Scholar
Hazlett, H. C., Poe, M. D., Gerig, G., Styner, M., Chappell, C., Smith, R. G., et al. (2011). Early brain overgrowth in autism associated with an increase in cortical surface area before age 2 years. Archives of General Psychiatry, 68, 467–476.Google Scholar
Herbert, M. R., Ziegler, D. A., Deutsch, C. K., O'Brien, L. M., Lange, N., Bakardjiev, A., et al. (2003). Dissociations of cerebral cortex, subcortical and cerebral white matter volumes in autistic boys. Brain, 126(Pt. 5), 1182–1192.Google Scholar
Hicks, C., Asfour, R., Pannuti, A., & Miele, L. (2011). An integrative genomics approach to biomarker discovery in breast cancer. Cancer Informatics, 10, 185–204.Google Scholar
Hill, J., Inder, T., Neil, J., Dierker, D., Harwell, J., & Van Essen, D. (2010). Similar patterns of cortical expansion during human development and evolution. Proceedings of the National Academy of Sciences, 107, 13135–13140.Google Scholar
Hu, B. Y., Weick, J. P., Yu, J., Ma, L. X., Zhang, X. Q., Thomson, J. A., et al. (2010). Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proceedings of the National Academy of Sciences, 107, 4335–4340.CrossRefGoogle ScholarPubMed
Jiang, Y., Henderson, D., Blackstad, M., Chen, A., Miller, R. F., & Verfaillie, C. M. (2003). Neuroectodermal differentiation from mouse multipotent adult progenitor cells. Proceedings of the National Academy of Sciences, 100(Suppl. 1), 11854–11860.Google Scholar
Johnson, M. B., Kawasawa, Y. I., Mason, C. E., Krsnik, Z., Coppola, G., Bogdanovic, D., et al. (2009). Functional and evolutionary insights into human brain development through global transcriptome analysis. Neuron, 62, 494–509.CrossRefGoogle ScholarPubMed
Kang, H. J., Kawasawa, Y. I., Cheng, F., Zhu, Y., Xu, X., Li, M., et al. (2011). Spatio-temporal transcriptome of the human brain. Nature, 478(7370), 483–489.CrossRefGoogle ScholarPubMed
Kanner, L., & Eisenberg, L. (1957). Early infantile autism, 1943–1955. Psychiatric Research Reports American Psychiatric Association, 7, 55–65.Google Scholar
Kim, J. E., O'Sullivan, M. L., Sanchez, C. A., Hwang, M., Israel, M. A., Brennand, K., et al. (2011). Investigating synapse formation and function using human pluripotent stem cell-derived neurons. Proceedings of the National Academy of Sciences, 108, 3005–3010.Google Scholar
Kranz, A., Wagner, D. C., Kamprad, M., Scholz, M., Schmidt, U. R., Nitzsche, F., et al. (2010). Transplantation of placenta-derived mesenchymal stromal cells upon experimental stroke in rats. Brain Research, 1315, 128–136.Google Scholar
Kriegstein, A., Noctor, S., & Martinez-Cerdeno, V. (2006). Patterns of neural stem and progenitor cell division may underlie evolutionary cortical expansion. Nature Reviews Neuroscience, 7, 883–890.Google Scholar
Langen, M., Schnack, H. G., Nederveen, H., Bos, D., Lahuis, B. E., de Jonge, M. V., et al. (2009). Changes in the developmental trajectories of striatum in autism. Biological Psychiatry, 66, 327–333.Google Scholar
Lawrence, Y. A., Kemper, T. L., Bauman, M. L., & Blatt, G. J. (2010). Parvalbumin-, calbindin-, and calretinin-immunoreactive hippocampal interneuron density in autism. Acta Neurologica Scandinavica, 121, 99–108.Google Scholar
Lee, H. J., Lee, J. K., Lee, H., Carter, J. E., Chang, J. W., Oh, W., et al. (2012). Human umbilical cord blood-derived mesenchymal stem cells improve neuropathology and cognitive impairment in an Alzheimer's disease mouse model through modulation of neuroinflammation. Neurobiology of Aging, 33, 588–602.Google Scholar
Lim, D. A., Flames, N., Collado, L., & Herrera, D. G. (2002). Investigating the use of primary adult subventricular zone neural precursor cells for neuronal replacement therapies. Brain Research Bulletin, 57, 759–764.Google Scholar
Lui, J. H., Hansen, D. V., & Kriegstein, A. R. (2011). Development and evolution of the human neocortex. Cell, 146, 18–36.Google Scholar
Maherali, N., & Hochedlinger, K. (2008). Guidelines and techniques for the generation of induced pluripotent stem cells. Cell Stem Cell, 3, 595–605.Google Scholar
Marchetto, M. C., Carromeu, C., Acab, A., Yu, D., Yeo, G. W., Mu, Y., et al. (2010). A model for neural development and treatment of rett syndrome using human induced pluripotent stem cells. Cell, 143, 527–539.CrossRefGoogle Scholar
Mariani, J., Simonini, M. V., Palejev, D., Tomasini, L., Coppola, G., Szekely, A., et al. (2012). Modeling human cortical development in vitro using induced pluripotent stem cells. Proceedings of the National Academy of Sciences, 109, 12770–12775.Google Scholar
Martinez-Cerdeno, V., Noctor, S. C., & Kriegstein, A. R. (2006). The role of intermediate progenitor cells in the evolutionary expansion of the cerebral cortex. Cerebral Cortex, 16(Suppl. 1), i152–i161.Google Scholar
Meissner, A., Wernig, M., & Jaenisch, R. (2007). Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells. Nature Biotechnology, 25, 1177–1181.CrossRefGoogle ScholarPubMed
Meng, X., Neises, A., Su, R. J., Payne, K. J., Ritter, L., Gridley, D. S., et al. (2012). Efficient reprogramming of human cord blood CD34+ cells into induced pluripotent stem cells with OCT4 and SOX2 alone. Molecular Therapy, 20, 408–416.Google Scholar
Mikkelsen, T. S., Ku, M., Jaffe, D. B., Issac, B., Lieberman, E., Giannoukos, G., et al. (2007). Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature, 448(7153), 553–560.CrossRefGoogle Scholar
Miles, J. H., Hadden, L. L., Takahashi, T. N., & Hillman, R. E. (2000). Head circumference is an independent clinical finding associated with autism. American Journal of Medical Genetics, 95, 339–350.Google Scholar
Milosevic, A., Noctor, S. C., Martinez-Cerdeno, V., Kriegstein, A. R., & Goldman, J. E. (2008). Progenitors from the postnatal forebrain subventricular zone differentiate into cerebellar-like interneurons and cerebellar-specific astrocytes upon transplantation. Molecular and Cellular Neurosciences, 39, 324–334.Google Scholar
Molnar, Z., Metin, C., Stoykova, A., Tarabykin, V., Price, D. J., Francis, F., et al. (2006). Comparative aspects of cerebral cortical development. European Journal of Neuroscience, 23, 921–934.Google Scholar
Momin, E. N., Mohyeldin, A., Zaidi, H. A., Vela, G., & Quinones-Hinojosa, A. (2010). Mesenchymal stem cells: new approaches for the treatment of neurological diseases. Current Stem Cell Research and Therapy, 5, 326–344.Google Scholar
Montgomery, S. B., Sammeth, M., Gutierrez-Arcelus, M., Lach, R. P., Ingle, C., Nisbett, J., et al. (2010). Transcriptome genetics using second generation sequencing in a Caucasian population. Nature, 464(7289), 773–777.Google Scholar
Myers, A. J., Gibbs, J. R., Webster, J. A., Rohrer, K., Zhao, A., Marlowe, L., et al. (2007). A survey of genetic human cortical gene expression. Nature Genetics, 39, 1494–1499.CrossRefGoogle ScholarPubMed
Okita, K., Matsumura, Y., Sato, Y., Okada, A., Morizane, A., Okamoto, S., et al. (2011). A more efficient method to generate integration-free human iPS cells. Nature Methods, 8, 409–412.CrossRefGoogle ScholarPubMed
Palmen, S. J., Hulshoff Pol, H. E., Kemner, C., Schnack, H. G., Durston, S., Lahuis, B. E., et al. (2005). Increased gray-matter volume in medication-naive high-functioning children with autism spectrum disorder. Psychological Medicine, 35, 561–570.Google Scholar
Palmen, S. J., & van Engeland, H. (2004). Review on structural neuroimaging findings in autism. Journal of Neural Transmission, 111, 903–929.Google Scholar
Palmen, S. J., van Engeland, H., Hof, P. R., & Schmitz, C. (2004). Neuropathological findings in autism. Brain, 127(Pt. 12), 2572–2583.CrossRefGoogle ScholarPubMed
Pasca, S. P., Portmann, T., Voineagu, I., Yazawa, M., Shcheglovitov, A., Pasca, A. M., et al. (2011). Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome. Nature Medicine, 17, 1657–1662.CrossRefGoogle ScholarPubMed
Pedrosa, E., Sandler, V., Shah, A., Carroll, R., Chang, C., Rockowitz, S., et al. (2011). Development of patient-specific neurons in schizophrenia using induced pluripotent stem cells. Journal of Neurogenetics, 25, 88–103.Google Scholar
Rakic, P. (1995). A small step for the cell, a giant leap for mankind: A hypothesis of neocortical expansion during evolution. Trends in Neurosciences, 18, 383–388.Google Scholar
Rakic, P. (2009). Evolution of the neocortex: A perspective from developmental biology. Nature Reviews Neuroscience, 10, 724–735.Google Scholar
Rash, B. G., Lim, H. D., Breunig, J. J., & Vaccarino, F. M. (2011). FGF signaling expands embryonic cortical surface area by regulating Notch-dependent neurogenesis. Journal of Neuroscience, 31, 15604–15617.Google Scholar
Rubenstein, J. L. R., Martinez, S., Shimamura, K., & Puelles, L. (1994). The embryonic vertebrate forebrain: The prosomeric model. Science, 266, 576–580.Google Scholar
Sbacchi, S., Acquadro, F., Calo, I., Cali, F., & Romano, V. (2010). Functional annotation of genes overlapping copy number variants in autistic patients: focus on axon pathfinding. Current Genomics, 11, 136–145.CrossRefGoogle ScholarPubMed
Schoof, N., Iles, M. M., Bishop, D. T., Newton-Bishop, J. A., & Barrett, J. H. (2011). Pathway-based analysis of a melanoma genome-wide association study: analysis of genes related to tumour-immunosuppression. PLoS One, 6, e29451.CrossRefGoogle ScholarPubMed
Schumann, C. M., & Amaral, D. G. (2006). Stereological analysis of amygdala neuron number in autism. Journal of Neuroscience, 26, 7674–7679.CrossRefGoogle ScholarPubMed
Schumann, C. M., Hamstra, J., Goodlin-Jones, B. L., Lotspeich, L. J., Kwon, H., Buonocore, M. H., et al. (2004). The amygdala is enlarged in children but not adolescents with autism; the hippocampus is enlarged at all ages. Journal of Neuroscience, 24, 6392–6401.CrossRefGoogle Scholar
Shepherd, G. M., & Katz, D. M. (2011). Synaptic microcircuit dysfunction in genetic models of neurodevelopmental disorders: Focus on Mecp2 and Met. Current Opinion in Neurobiology, 21, 827–833.Google Scholar
Si-Tayeb, K., Noto, F. K., Sepac, A., Sedlic, F., Bosnjak, Z. J., Lough, J. W., et al. (2010). Generation of human induced pluripotent stem cells by simple transient transfection of plasmid DNA encoding reprogramming factors. BMC Developmental Biology, 10, 81.Google Scholar
Simeone, A., Acampora, D., Gulisano, M., Stornaiuolo, A., & Boncinelli, E. (1992). Nested expression domains of four homeobox genes in developing rostral brain. Nature, 358, 687–690.Google Scholar
Simonson, M. A., Wills, A. G., Keller, M. C., & McQueen, M. B. (2011). Recent methods for polygenic analysis of genome-wide data implicate an important effect of common variants on cardiovascular disease risk. BMC Medical Genetics, 12, 146.Google Scholar
Sowell, E. R., Kan, E., Yoshii, J., Thompson, P. M., Bansal, R., Xu, D., et al. (2008). Thinning of sensorimotor cortices in children with Tourette syndrome. Nature Neuroscience, 11, 637–639.Google Scholar
Staerk, J., Dawlaty, M. M., Gao, Q., Maetzel, D., Hanna, J., Sommer, C. A., et al. (2010). Reprogramming of human peripheral blood cells to induced pluripotent stem cells. Cell Stem Cell, 7, 20–24.Google Scholar
Stevens, H. E., Smith, K. M., Rash, B. G., & Vaccarino, F. M. (2010). Neural stem cell regulation, fibroblast growth factors, and the developmental origins of neuropsychiatric disorders. Frontiers in Neuroscience, 4, 59.Google Scholar
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., et al. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131, 861–872.Google Scholar
Tam, P. P. (1989). Regionalisation of the mouse embryonic ectoderm: Allocation of prospective ectodermal tissues during gastrulation. Development, 107, 55–67.CrossRefGoogle ScholarPubMed
Trzaska, K. A., King, C. C., Li, K. Y., Kuzhikandathil, E. V., Nowycky, M. C., Ye, J. H., et al. (2009). Brain-derived neurotrophic factor facilitates maturation of mesenchymal stem cell-derived dopamine progenitors to functional neurons. Journal of Neurochemistry, 110, 1058–1069.Google Scholar
Vaccarino, F. M., Ganat, Y., Zhang, Y., & Zheng, W. (2001). Stem cells in neurodevelopment and plasticity. Neuropsychopharmacology, 25, 805–815.Google Scholar
Vaccarino, F. M., Grigorenko, E. L., Smith, K. M., & Stevens, H. E. (2009). Regulation of cerebral cortical size and neuron number by fibroblast growth factors: Implications for autism. Journal of Autism and Developmental Disorders, 39, 511–520.Google Scholar
Vaccarino, F. M., Stevens, H. E., Kocabas, A., Palejev, D., Szekely, A., Grigorenko, E. L., et al. (2011). Induced pluripotent stem cells: A new tool to confront the challenge of neuropsychiatric disorders. Neuropharmacology, 60, 1355–1363.Google Scholar
Vaccarino, F. M., Urban, A. E., Stevens, H. E., Szekely, A., Abyzov, A., Grigorenko, E. L., et al. (2011). Annual research review: The promise of stem cell research for neuropsychiatric disorders. Journal of Child Psychology and Psychiatry, 52, 504–516.CrossRefGoogle ScholarPubMed
Wang, F., Yasuhara, T., Shingo, T., Kameda, M., Tajiri, N., Yuan, W. J., et al. (2010). Intravenous administration of mesenchymal stem cells exerts therapeutic effects on parkinsonian model of rats: Focusing on neuroprotective effects of stromal cell-derived factor-1alpha. BMC Neuroscience, 11, 52.Google Scholar
Warren, L., Manos, P. D., Ahfeldt, T., Loh, Y. H., Li, H., Lau, F., et al. (2010). Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell, 7, 618–630.Google Scholar
Weng, L., Macciardi, F., Subramanian, A., Guffanti, G., Potkin, S. G., Yu, Z., et al. (2011). SNP-based pathway enrichment analysis for genome-wide association studies. BMC Bioinformatics, 12, 99.Google Scholar
Wernig, M., Meissner, A., Foreman, R., Brambrink, T., Ku, M., Hochedlinger, K., et al. (2007). In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature, 448(7151), 318–324.CrossRefGoogle ScholarPubMed
Wilmut, I., Schnieke, A. E., McWhir, J., Kind, A. J., & Campbell, K. H. (1997). Viable offspring derived from fetal and adult mammalian cells. Nature, 385(6619), 810–813.Google Scholar
Withington, S., Beddington, R., & Cooke, J. (2001). Foregut endoderm is required at head process stages for anteriormost neural patterning in chick. Development, 128, 309–320.Google Scholar
Woodhouse, W., Bailey, A., Rutter, M., Bolton, P., Baird, G., & Le Couteur, A. (1996). Head circumference in autism and other pervasive developmental disorders. Journal of Child Psychology and Psychiatry, 37, 665–671.Google Scholar
Xia, G., Hong, X., Chen, X., Lan, F., Zhang, G., & Liao, L. (2010). Intracerebral transplantation of mesenchymal stem cells derived from human umbilical cord blood alleviates hypoxic ischemic brain injury in rat neonates. Journal of Perinatal Medicine, 38, 215–221.Google Scholar
Xiong, Q., Ancona, N., Hauser, E. R., Mukherjee, S., & Furey, T. S. (2012). Integrating genetic and gene expression evidence into genome-wide association analysis of gene sets. Genome Research, 22, 386–397.CrossRefGoogle ScholarPubMed
Yaspan, B. L., Bush, W. S., Torstenson, E. S., Ma, D., Pericak-Vance, M. A., Ritchie, M. D., et al. (2011). Genetic analysis of biological pathway data through genomic randomization. Human Genetics, 129, 563–571.Google Scholar
Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J. L., Tian, S., et al. (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science, 318(5858), 1917–1920.Google Scholar
Zhong, H., Yang, X., Kaplan, L. M., Molony, C., & Schadt, E. E. (2010). Integrating pathway analysis and genetics of gene expression for genome-wide association studies. American Journal of Human Genetics, 86, 581–591.Google Scholar
Zhou, J., & Parada, L. F. (2012). PTEN signaling in autism spectrum disorders. Current Opinion in Neurobiology. Advance online publication. doi:10.1016/j.conb.2012.05.004Google Scholar