TY - JOUR
T1 - Monkey hybrid stem cells develop cellular features of Huntington's disease
AU - Laowtammathron, Chuti
AU - Cheng, Eric C.H.
AU - Cheng, Pei Hsun
AU - Snyder, Brooke R.
AU - Yang, Shang Hsun
AU - Johnson, Zach
AU - Lorthongpanich, Chanchao
AU - Kuo, Hung Chih
AU - Parnpai, Rangsun
AU - Chan, Anthony W.S.
N1 - Funding Information:
We thank the following members at Dr. Chan’s laboratory, Nateewan Udomsil and Dr. Mariena Ketudat-Cairns for assistance in statistical analysis, the veterinary staff and the animal resource at the Yerkes National Primate Research Center (YNPRC), Cell Line Genetics LLC for Cytogenetic analysis, and the critical review provided by Dr. Xiao-Jiang Li and Leslee Sinclair. mEM48 was provided by Dr. Xiao-Jiang Li. Acryline was provided by NICHD/ NIH. All procedures were approved by YNPRC/Emory Animal Care and Biosafety Committees. 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. AWSC is supported by the NCRR at NIH (5 R24 RR018827-06).
PY - 2010/2/5
Y1 - 2010/2/5
N2 - 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.
AB - 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.
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U2 - 10.1186/1471-2121-11-12
DO - 10.1186/1471-2121-11-12
M3 - Article
C2 - 20132560
AN - SCOPUS:77949503567
SN - 1471-2121
VL - 11
JO - BMC Cell Biology
JF - BMC Cell Biology
M1 - 12
ER -