Monkey hybrid stem cells develop cellular features of Huntington's disease.
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.
Yerkes National Primate Research Center, 954 Gatewood Rd, NE Atlanta, GA 39329, USA.
Chuti
C
Laowtammathron
Eric Ch
ECh
Cheng
Pei-Hsun
PH
Cheng
Brooke R
BR
Snyder
Shang-Hsun
SH
Yang
Zach
Z
Johnson
Chanchao
C
Lorthongpanich
Hung-Chih
HC
Kuo
Rangsun
R
Parnpai
Anthony W S
AW
Chan
D000818:Animals; D002454:Cell Differentiation; D004622:Embryo, Mammalian; D005838:Genotype; D000882:Haplorhini; D006816:Huntington Disease / Q000378:metabolism / Q000473:pathology*; D006822:Hybrid Cells; D007621:Karyotyping; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology; D013234:Stem Cells / Q000166:cytology*
D008869:Microtubule-Associated Proteins