Human Huntington’s Disease iPSC-Derived Cortical Neurons Display Altered Transcriptomics, Morphology, and Maturation
Shagun R. Mehta,
Colton M. Tom,
Yizhou Wang,
Catherine Bresee,
David Rushton,
Pranav P. Mathkar,
Jie Tang,
Virginia B. Mattis
Affiliations
Shagun R. Mehta
The Board of Governor’s Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Colton M. Tom
The Board of Governor’s Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Yizhou Wang
Genomics Core Facility, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Catherine Bresee
Biostatistics & Bioinformatics Research Center, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
David Rushton
The Board of Governor’s Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Pranav P. Mathkar
The Board of Governor’s Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Jie Tang
Genomics Core Facility, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Virginia B. Mattis
The Board of Governor’s Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Corresponding author
Summary: Huntington’s disease (HD) is a neurodegenerative disease caused by an expanded CAG repeat in the Huntingtin (HTT) gene. Induced pluripotent stem cell (iPSC) models of HD provide an opportunity to study the mechanisms underlying disease pathology in disease-relevant patient tissues. Murine studies have demonstrated that HTT is intricately involved in corticogenesis. However, the effect of mutant Hungtintin (mtHTT) in human corticogenesis has not yet been thoroughly explored. This examination is critical, due to inherent differences in cortical development and timing between humans and mice. We therefore differentiated HD and non-diseased iPSCs into functional cortical neurons. While HD patient iPSCs can successfully differentiate toward a cortical fate in culture, the resulting neurons display altered transcriptomics, morphological and functional phenotypes indicative of altered corticogenesis in HD. : Mehta et al. show that induced pluripotent stem cells (iPSCs) from Huntington’s disease (HD) patients can successfully differentiate into functional cerebral cortical neurons. However, the resulting HD cortical neurons display altered transcriptomics and morphological and functional phenotypes indicative of altered corticogenesis in HD. Keywords: Huntington’s disease, iPSC, differentiation, cerebral cortex, corticogenesis, Huntingtin
