Ross, C.A. et al. Huntington disease: natural history, biomarkers and prospects for therapeutics. Nat. Rev. Neurol. 10, 204–216 (2014).
Bates, G.P. et al. Huntington disease. Nat. Rev. Dis. Primers 1, 15005 (2015).
Wexler, N.S. et al. Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset. Proc. Natl. Acad. Sci. USA 101, 3498–3503 (2004).
Marder, K. & Mehler, M.F. Development and neurodegeneration: turning HD pathogenesis on its head. Neurology 79, 621–622 (2012).
Curtis, M.A., Kam, M. & Faull, R.L. Neurogenesis in humans. Eur. J. Neurosci. 33, 1170–1174 (2011).
Curtis, M.A. et al. Increased cell proliferation and neurogenesis in the adult human Huntington's disease brain. Proc. Natl. Acad. Sci. USA 100, 9023–9027 (2003).
Ernst, A. et al. Neurogenesis in the striatum of the adult human brain. Cell 156, 1072–1083 (2014).
Aylward, E.H. et al. Regional atrophy associated with cognitive and motor function in prodromal Huntington disease. J. Huntingtons Dis. 2, 477–489 (2013).
Niccolini, F. & Politis, M. Neuroimaging in Huntington's disease. World J. Radiol. 6, 301–312 (2014).
Scahill, R.I. et al. Clinical impairment in premanifest and early Huntington's disease is associated with regionally specific atrophy. Hum. Brain Mapp. 34, 519–529 (2013).
Lee, J.K. et al. Measures of growth in children at risk for Huntington disease. Neurology 79, 668–674 (2012).
Imaizumi, Y. & Okano, H. Modeling human neurological disorders with induced pluripotent stem cells. J. Neurochem. 129, 388–399 (2014).
Pei, Y. et al. Comparative neurotoxicity screening in human iPSC-derived neural stem cells, neurons and astrocytes. Brain Res. 1638, 57–73 (2016).
HD iPSC Consortium. Induced pluripotent stem cells from patients with Huntington's disease show CAG-repeat-expansion-associated phenotypes. Cell Stem Cell 11, 264–278 (2012).
Mattis, V.B. et al. HD iPSC-derived neural progenitors accumulate in culture and are susceptible to BDNF withdrawal due to glutamate toxicity. Hum. Mol. Genet. 24, 3257–3271 (2015).
Gourfinkel-An, I. et al. Changes in GAD67 mRNA expression evidenced by in situ hybridization in the brain of R6/2 transgenic mice. J. Neurochem. 86, 1369–1378 (2003).
Marcora, E., Gowan, K. & Lee, J.E. Stimulation of NeuroD activity by huntingtin and huntingtin-associated proteins HAP1 and MLK2. Proc. Natl. Acad. Sci. USA 100, 9578–9583 (2003).
Kintner, C. Neurogenesis in embryos and in adult neural stem cells. J. Neurosci. 22, 639–643 (2002).
Gao, Z. et al. Neurod1 is essential for the survival and maturation of adult-born neurons. Nat. Neurosci. 12, 1090–1092 (2009).
Buckley, N.J., Johnson, R., Zuccato, C., Bithell, A. & Cattaneo, E. The role of REST in transcriptional and epigenetic dysregulation in Huntington's disease. Neurobiol. Dis. 39, 28–39 (2010).
Rodenas-Ruano, A., Chávez, A.E., Cossio, M.J., Castillo, P.E. & Zukin, R.S. REST-dependent epigenetic remodeling promotes the developmental switch in synaptic NMDA receptors. Nat. Neurosci. 15, 1382–1390 (2012).
Dias, J.M., Alekseenko, Z., Applequist, J.M. & Ericson, J. Tgfβ signaling regulates temporal neurogenesis and potency of neural stem cells in the CNS. Neuron 84, 927–939 (2014).
Ring, K.L. et al. Genomic analysis reveals disruption of striatal neuronal development and therapeutic targets in human Huntington's disease neural stem cells. Stem Cell Reports 5, 1023–1038 (2015).
Bashaw, G.J. & Klein, R. Signaling from axon guidance receptors. Cold Spring Harb. Perspect. Biol. 2, a001941 (2010).
West, A.E. & Greenberg, M.E. Neuronal activity-regulated gene transcription in synapse development and cognitive function. Cold Spring Harb. Perspect. Biol. 3, a005744 (2011).
Onorati, M. et al. Molecular and functional definition of the developing human striatum. Nat. Neurosci. 17, 1804–1815 (2014).
Glajch, K.E. & Sadri-Vakili, G. Epigenetic mechanisms involved in Huntington's disease pathogenesis. J. Huntingtons Dis. 4, 1–15 (2015).
Hsieh, J. & Gage, F.H. Chromatin remodeling in neural development and plasticity. Curr. Opin. Cell Biol. 17, 664–671 (2005).
Vashishtha, M. et al. Targeting H3K4 trimethylation in Huntington disease. Proc. Natl. Acad. Sci. USA 110, E3027–E3036 (2013).
Lynch, G., Rex, C.S. & Gall, C.M. LTP consolidation: substrates, explanatory power, and functional significance. Neuropharmacology 52, 12–23 (2007).
Schneider, J.W. et al. Small-molecule activation of neuronal cell fate. Nat. Chem. Biol. 4, 408–410 (2008).
Ferrante, R.J., Kowall, N.W. & Richardson, E.P. Jr. Proliferative and degenerative changes in striatal spiny neurons in Huntington's disease: a combined study using the section-Golgi method and calbindin D28k immunocytochemistry. J. Neurosci. 11, 3877–3887 (1991).
Fedele, V., Roybon, L., Nordström, U., Li, J.Y. & Brundin, P. Neurogenesis in the R6/2 mouse model of Huntington's disease is impaired at the level of NeuroD1. Neuroscience 173, 76–81 (2011).
Mangiarini, L. et al. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87, 493–506 (1996).
Marco, S. et al. Suppressing aberrant GluN3A expression rescues synaptic and behavioral impairments in Huntington's disease models. Nat. Med. 19, 1030–1038 (2013).
Covey, M.V., Streb, J.W., Spektor, R. & Ballas, N. REST regulates the pool size of the different neural lineages by restricting the generation of neurons and oligodendrocytes from neural stem/progenitor cells. Development 139, 2878–2890 (2012).
Conaco, C., Otto, S., Han, J.J. & Mandel, G. Reciprocal actions of REST and a microRNA promote neuronal identity. Proc. Natl. Acad. Sci. USA 103, 2422–2427 (2006).
Achour, M. et al. Neuronal identity genes regulated by super-enhancers are preferentially down-regulated in the striatum of Huntington's disease mice. Hum. Mol. Genet. 24, 3481–3496 (2015).
Bai, G. et al. Epigenetic dysregulation of hairy and enhancer of split 4 (HES4) is associated with striatal degeneration in postmortem Huntington brains. Hum. Mol. Genet. 24, 1441–1456 (2015).
Waldvogel, H.J. & Faull, R.L. The diversity of GABAA receptor subunit distribution in the normal and Huntington's disease human brain. Adv. Pharmacol. 73, 223–264 (2015).
Curtis, M.A., Waldvogel, H.J., Synek, B. & Faull, R.L. A histochemical and immunohistochemical analysis of the subependymal layer in the normal and Huntington's disease brain. J. Chem. Neuroanat. 30, 55–66 (2005).
Lorincz, M.T. & Zawistowski, V.A. Expanded CAG repeats in the murine Huntington's disease gene increases neuronal differentiation of embryonic and neural stem cells. Mol. Cell. Neurosci. 40, 1–13 (2009).
Blockx, I. et al. Microstructural changes observed with DKI in a transgenic Huntington rat model: evidence for abnormal neurodevelopment. Neuroimage 59, 957–967 (2012).
Molero, A.E. et al. Impairment of developmental stem cell-mediated striatal neurogenesis and pluripotency genes in a knock-in model of Huntington's disease. Proc. Natl. Acad. Sci. USA 106, 21900–21905 (2009).
Labadorf, A. et al. RNA sequence analysis of human Huntington disease brain reveals an extensive increase in inflammatory and developmental gene expression. PLoS One 10, e0143563 (2015).
Molero, A.E. et al. Selective expression of mutant huntingtin during development recapitulates characteristic features of Huntington's disease. Proc. Natl. Acad. Sci. USA 113, 5736–5741 (2016).
Langfelder, P. et al. Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice. Nat. Neurosci. 19, 623–633 (2016).
Novak, M.J. et al. Basal ganglia-cortical structural connectivity in Huntington's disease. Hum. Brain Mapp. 36, 1728–1740 (2015).
Chang, L. et al. Gray matter maturation and cognition in children with different APOE ɛ genotypes. Neurology 87, 585–594 (2016).
Hsieh, J. & Schneider, J.W. Neuroscience. Neural stem cells, excited. Science 339, 1534–1535 (2013).
Luong, M.X. et al. A call for standardized naming and reporting of human ESC and iPSC lines. Cell Stem Cell 8, 357–359 (2011).
Sareen, D. et al. Inhibition of apoptosis blocks human motor neuron cell death in a stem cell model of spinal muscular atrophy. PLoS One 7, e39113 (2012).
Okita, K. et al. A more efficient method to generate integration-free human iPS cells. Nat. Methods 8, 409–412 (2011).
Müller, F.J. et al. A bioinformatic assay for pluripotency in human cells. Nat. Methods 8, 315–317 (2011).
Ebert, A.D. et al. EZ spheres: a stable and expandable culture system for the generation of pre-rosette multipotent stem cells from human ESCs and iPSCs. Stem Cell Res. 10, 417–427 (2013).
Banerjee, A. & A monoclonal antibody against the type II isotype of beta-tubulin. Preparation of isotypically altered tubulin. J. Biol. Chem. 263, 3029–3034 (1988).
Scholzen, T. & Gerdes, J. The Ki-67 protein: from the known and the unknown. J. Cell. Physiol. 182, 311–322 (2000).
Reske-Nielsen, E., Oster, S. & Reintoft, I. Astrocytes in the prenatal central nervous system. From 5th to 28th week of gestation. An immunohistochemical study on paraffin-embedded material. Acta Pathol. Microbiol. Immunol. Scand. [A] 95, 339–346 (1987).
Oh, D. & Prayson, R.A. Evaluation of epithelial and keratin markers in glioblastoma multiforme: an immunohistochemical study. Arch. Pathol. Lab. Med. 123, 917–920 (1999).
Binder, L.I., Frankfurter, A. & Rebhun, L.I. Differential localization of MAP-2 and tau in mammalian neurons in situ. Ann. NY Acad. Sci. 466, 145–166 (1986).
Jung, E.S. et al. Jmjd2C increases MyoD transcriptional activity through inhibiting G9a-dependent MyoD degradation. Biochim. Biophys. Acta 1849, 1081–1094 (2015).
Imai, Y., Ibata, I., Ito, D., Ohsawa, K. & Kohsaka, S. A novel gene iba1 in the major histocompatibility complex class III region encoding an EF hand protein expressed in a monocytic lineage. Biochem. Biophys. Res. Commun. 224, 855–862 (1996).
Sneddon, J.B., Borowiak, M. & Melton, D.A. Self-renewal of embryonic-stem-cell-derived progenitors by organ-matched mesenchyme. Nature 491, 765–768 (2012).
Miyawaki, S. et al. Tumour resistance in induced pluripotent stem cells derived from naked mole-rats. Nat. Commun. 7, 11471 (2016).
Thanasupawat, T. et al. Platinum (IV) coiled coil nanotubes selectively kill human glioblastoma cells. Nanomedicine (Lond.) 11, 913–925 (2015).
Gowing, G. et al. Glial cell line-derived neurotrophic factor-secreting human neural progenitors show long-term survival, maturation into astrocytes, and no tumor formation following transplantation into the spinal cord of immunocompromised rats. Neuroreport 25, 367–372 (2014).
Smagin, D.A. et al. Altered hippocampal neurogenesis and amygdalar neuronal activity in adult mice with repeated experience of aggression. Front Neurosci. 9, 443 (2015).
Figueres-Oñate, M. & López-Mascaraque, L. Adult olfactory bulb interneuron phenotypes identified by targeting embryonic and postnatal neural progenitors. Front. Neurosci. 10, 194 (2016).
Livak, K.J. & Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔC(T) method. Methods 25, 402–408 (2001).
Shah, A.R. et al. Enabling high-throughput data management for systems biology: the Bioinformatics Resource Manager. Bioinformatics 23, 906–909 (2007).
Sturn, A., Quackenbush, J. & Trajanoski, Z. Genesis: cluster analysis of microarray data. Bioinformatics 18, 207–208 (2002).
Egelhofer, T.A. et al. An assessment of histone-modification antibody quality. Nat. Struct. Mol. Biol. 18, 91–93 (2011).
Zhang, Y. et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 9, R137 (2008).
Shao, Z., Zhang, Y., Yuan, G.C., Orkin, S.H. & Waxman, D.J. MAnorm: a robust model for quantitative comparison of ChIP-Seq data sets. Genome Biol. 13, R16 (2012).
Hashimoto, T.B., Edwards, M.D. & Gifford, D.K. Universal count correction for high-throughput sequencing. PLoS Comput. Biol. 10, e1003494 (2014).
Macisaac, K.D. et al. A hypothesis-based approach for identifying the binding specificity of regulatory proteins from chromatin immunoprecipitation data. Bioinformatics 22, 423–429 (2006).
Roider, H.G., Lenhard, B., Kanhere, A., Haas, S.A. & Vingron, M. CpG-depleted promoters harbor tissue-specific transcription factor binding signals—implications for motif overrepresentation analyses. Nucleic Acids Res. 37, 6305–6315 (2009).
Wingender, E., Dietze, P., Karas, H. & Knüppel, R. TRANSFAC: a database on transcription factors and their DNA binding sites. Nucleic Acids Res. 24, 238–241 (1996).
Telezhkin, V. et al. Forced cell cycle exit and modulation of GABAA, CREB, and GSK3β signaling promote functional maturation of induced pluripotent stem cell-derived neurons. Am. J. Physiol. Cell Physiol. 310, C520–C541 (2016).
Sun, J., Liu, Y., Moreno, S., Baudry, M. & Bi, X. Imbalanced mechanistic target of rapamycin C1 and C2 activity in the cerebellum of Angelman syndrome mice impairs motor function. J. Neurosci. 35, 4706–4718 (2015).
Wu, C. et al. Talpid3-binding centrosomal protein Cep120 is required for centriole duplication and proliferation of cerebellar granule neuron progenitors. PLoS One 9, e107943 (2014).
Shi, C.H. et al. Ataxia and hypogonadism caused by the loss of ubiquitin ligase activity of the U box protein CHIP. Hum. Mol. Genet. 23, 1013–1024 (2014).
Zhang, Y. et al. Electroacupuncture improves cognitive ability following cerebral ischemia reperfusion injury via CaM-CaMKIV-CREB signaling in the rat hippocampus. Exp. Ther. Med. 12, 777–782 (2016).
Zheng, J. et al. Inhibitory receptors bind ANGPTLs and support blood stem cells and leukaemia development. Nature 485, 656–660 (2012).
Ochaba, J. et al. PIAS1 regulates mutant huntingtin accumulation and Huntington's disease-associated phenotypes in vivo. Neuron 90, 507–520 (2016).
Hong, S. et al. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science 352, 712–716 (2016).
Arrasate, M., Mitra, S., Schweitzer, E.S., Segal, M.R. & Finkbeiner, S. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 431, 805–810 (2004).
Barmada, S.J. et al. Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models. Nat. Chem. Biol. 10, 677–685 (2014).
Skibinski, G., Nakamura, K., Cookson, M.R. & Finkbeiner, S. Mutant LRRK2 toxicity in neurons depends on LRRK2 levels and synuclein but not kinase activity or inclusion bodies. J. Neurosci. 34, 418–433 (2014).
Hockly, E., Woodman, B., Mahal, A., Lewis, C.M. & Bates, G. Standardization and statistical approaches to therapeutic trials in the R6/2 mouse. Brain Res. Bull. 61, 469–479 (2003).