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Niclis JC, Pinar A, Haynes JM, et al. Characterization of forebrain neurons derived from late-onset Huntington's disease human embryonic stem cell lines. Front Cell Neurosci. 2013;7:37doi: 10.3389/fncel.2013.00037.
Niclis, J. C., Pinar, A., Haynes, J. M., Alsanie, W., Jenny, R., Dottori, M., & Cram, D. S. (2013). Characterization of forebrain neurons derived from late-onset Huntington's disease human embryonic stem cell lines. Frontiers in cellular neuroscience, 737. https://doi.org/10.3389/fncel.2013.00037
Niclis, Jonathan C, et al. "Characterization of forebrain neurons derived from late-onset Huntington's disease human embryonic stem cell lines." Frontiers in cellular neuroscience vol. 7 (2013): 37. doi: https://doi.org/10.3389/fncel.2013.00037
Niclis JC, Pinar A, Haynes JM, Alsanie W, Jenny R, Dottori M, Cram DS. Characterization of forebrain neurons derived from late-onset Huntington's disease human embryonic stem cell lines. Front Cell Neurosci. 2013 Apr 05;7:37. doi: 10.3389/fncel.2013.00037. eCollection 2013. PMID: 23576953; PMCID: PMC3617399.
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Front Cell Neurosci. 2013 Apr 05;7:37. doi: 10.3389/fncel.2013.00037. eCollection 2013.

Characterization of forebrain neurons derived from late-onset Huntington's disease human embryonic stem cell lines.

Frontiers in cellular neuroscience

Jonathan C Niclis, Anita Pinar, John M Haynes, Walaa Alsanie, Robert Jenny, Mirella Dottori, David S Cram

Affiliations

  1. Monash Immunology and Stem Cell Laboratories, Monash University Clayton, VIC, Australia ; The Florey Institute of Neuroscience and Mental Health, University of Melbourne Parkville, VIC, Australia.

PMID: 23576953 PMCID: PMC3617399 DOI: 10.3389/fncel.2013.00037

Abstract

Huntington's disease (HD) is an incurable neurodegenerative disorder caused by a CAG repeat expansion in exon 1 of the Huntingtin (HTT) gene. Recently, induced pluripotent stem cell (iPSC) lines carrying atypical and aggressive (CAG60+) HD variants have been generated and exhibit disparate molecular pathologies. Here we investigate two human embryonic stem cell (hESC) lines carrying CAG37 and CAG51 typical late-onset repeat expansions in comparison to wildtype control lines during undifferentiated states and throughout forebrain neuronal differentiation. Pluripotent HD lines demonstrate growth, viability, pluripotent gene expression, mitochondrial activity and forebrain specification that is indistinguishable from control lines. Expression profiles of crucial genes known to be dysregulated in HD remain unperturbed in the presence of mutant protein and throughout differentiation; however, elevated glutamate-evoked responses were observed in HD CAG51 neurons. These findings suggest typical late-onset HD mutations do not alter pluripotent parameters or the capacity to generate forebrain neurons, but that such progeny may recapitulate hallmarks observed in established HD model systems. Such HD models will help further our understanding of the cascade of pathological events leading to disease onset and progression, while simultaneously facilitating the identification of candidate HD therapeutics.

Keywords: GABAergic neurons; Huntington's disease; human embryonic stem cells; neuronal differentiation

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