Monkey hybrid stem cells develop cellular features of Huntington's disease

• Type of Material: Article
• Authors: Chuti Laowtammathron, Emory University; Eric Cheng, Emory University; Pei-Hsun Cheng, Emory University; Brooke R. Snyder, Emory University; Shang-Hsun Yang, Emory University; Zachary Peter Johnson, Emory University; Chanchao Lorthongpanich, Suranaree University of Technology; Hung-Chih Kuo, Academia Sinica; Rangsun Parnpai, Suranaree University of Technology; Anthony Chan, Emory University
• Language: English
• Date: 2010
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: ©2010 Laowtammathron et al; licensee BioMed Central Ltd.
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://www.biomedcentral.com/1471-2121/11/12
• Title of Journal or Parent Work: BMC Cell Biology
• ISSN: 1471-2121
• Volume: 11
• Start Page: 12
• End Page: 12
• Grant/Funding Information: AWSC is supported by the NCRR at NIH (5 R24 RR018827-06).; The YNPRC is supported by the base grant RR-00165 awarded by the Animal Resources Program of the NIH.; CL and RP were supported by the Royal Golden Jubilee Ph.D program of Thailand Research Fund.
• Research Categories: Biology, Neuroscience

Abstract

Background Pluripotent stem cells that are capable of differentiating into different cell types and develop robust hallmark cellular features are useful tools for clarifying the impact of developmental events on neurodegenerative diseases such as Huntington's disease. Additionally, a Huntington's cell model that develops robust pathological features of Huntington's disease would be valuable for drug discovery research. Results To test this hypothesis, a pluripotent Huntington's disease monkey hybrid cell line (TrES1) was established from a tetraploid Huntington's disease monkey blastocyst generated by the fusion of transgenic Huntington's monkey skin fibroblast and a wild-type non-transgenic monkey oocyte. The TrES1 developed key Huntington's disease cellular pathological features that paralleled neural development. It expressed mutant huntingtin and stem cell markers, was capable of differentiating to neural cells, and developed teratoma in severely compromised immune deficient (SCID) mice. Interestingly, the expression of mutant htt, the accumulation of oligomeric mutant htt and the formation of intranuclear inclusions paralleled neural development in vitro , and even mutant htt was ubiquitously expressed. This suggests the development of Huntington's disease cellular features is influenced by neural developmental events. Conclusions Huntington's disease cellular features is influenced by neural developmental events. These results are the first to demonstrate that a pluripotent stem cell line is able to mimic Huntington's disease progression that parallels neural development, which could be a useful cell model for investigating the developmental impact on Huntington's disease pathogenesis.