title: Reversal of cellular phenotypes in neural cells derived from Huntington's disease monkey-induced pluripotent stem cells.
abstract: Huntington's disease (HD) is a dominant neurodegenerative disorder caused by the expansion of glutamine residues in the N-terminal region of the huntingtin (HTT) protein. The disease results in progressive neuronal loss, leading to motor, cognitive, and psychiatric impairment. Here, we report the establishment of neural progenitor cell (NPC) lines derived from induced pluripotent stem cells (iPSCs) of transgenic HD monkeys. Upon differentiation to neurons, HD neural cells develop cellular features of HD, including the formation of nuclear inclusions and oligomeric mutant HTT (mHTT) aggregates, as well as increased apoptosis. These phenotypes are rescued by genetic suppression of HTT and pharmacological treatment, demonstrating the ability of our HD cell model to respond to therapeutic treatment. The development and reversal of HD-associated phenotypes in neural cells from HD monkeys provides a unique nonhuman primate (NHP) model for exploring HD pathogenesis and evaluating therapeutics that could be assessed further in HD monkeys.
authors.affiliation: Yerkes National Primate Research Center, Atlanta, GA 39329, USA; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA; Genetics and Molecular Biology Program, Emory Laney Graduate School, Atlanta, GA 30322, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Carter
authors.affiliation: Yerkes National Primate Research Center, Atlanta, GA 39329, USA; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Yiju
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Yerkes National Primate Research Center, Atlanta, GA 39329, USA; Embryo Technology and Stem Cell Research Center, School of Biotechnology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
authors.forename: Tanut
authors.initials: T
authors.lastname: Kunkanjanawan
authors.affiliation: Yerkes National Primate Research Center, Atlanta, GA 39329, USA; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Yerkes National Primate Research Center, Atlanta, GA 39329, USA; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Moran
authors.affiliation: Yerkes National Primate Research Center, Atlanta, GA 39329, USA; Embryo Technology and Stem Cell Research Center, School of Biotechnology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
authors.forename: Kittiphong
authors.initials: K
authors.lastname: Putkhao
authors.affiliation: Yerkes National Primate Research Center, Atlanta, GA 39329, USA; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Jinjing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Oral Pathology, School of Dentistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan, Republic of China.
authors.forename: Anderson H C
authors.initials: AH
authors.lastname: Huang
authors.affiliation: Embryo Technology and Stem Cell Research Center, School of Biotechnology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
authors.forename: Rangsun
authors.initials: R
authors.lastname: Parnpai
authors.affiliation: Yerkes National Primate Research Center, Atlanta, GA 39329, USA; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA; Genetics and Molecular Biology Program, Emory Laney Graduate School, Atlanta, GA 30322, USA. Electronic address: awchan@emory.edu.
authors.forename: Anthony W S
authors.initials: AW
authors.lastname: Chan
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D017209:Apoptosis; D002478:Cells, Cultured; D059330:GABAergic Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000882:Haplorhini; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D008559:Memantine / Q000494:pharmacology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis; D010641:Phenotype
chemical_list: D000978:Antiparkinson Agents; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D008559:Memantine