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

Chuti Laowtammathron, Eric C.H. Cheng, Pei Hsun Cheng, Brooke R. Snyder, Shang-Hsun Yang, Zach Johnson, Chanchao Lorthongpanich, Hung Chih Kuo, Rangsun Parnpai, Anthony W.S. Chan

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Article number12
JournalBMC Cell Biology
Volume11
DOIs
Publication statusPublished - 2010 Feb 5

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Hybrid Cells
Huntington Disease
Haplorhini
Stem Cells
Pluripotent Stem Cells
Intranuclear Inclusion Bodies
Cell Line
Tetraploidy
Teratoma
Blastocyst
Drug Discovery
Neurodegenerative Diseases
Oocytes
Disease Progression
Fibroblasts
Skin

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Laowtammathron, C., Cheng, E. C. H., Cheng, P. H., Snyder, B. R., Yang, S-H., Johnson, Z., ... Chan, A. W. S. (2010). Monkey hybrid stem cells develop cellular features of Huntington's disease. BMC Cell Biology, 11, [12]. https://doi.org/10.1186/1471-2121-11-12
Laowtammathron, Chuti ; Cheng, Eric C.H. ; Cheng, Pei Hsun ; Snyder, Brooke R. ; Yang, Shang-Hsun ; Johnson, Zach ; Lorthongpanich, Chanchao ; Kuo, Hung Chih ; Parnpai, Rangsun ; Chan, Anthony W.S. / Monkey hybrid stem cells develop cellular features of Huntington's disease. In: BMC Cell Biology. 2010 ; Vol. 11.
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Laowtammathron, C, Cheng, ECH, Cheng, PH, Snyder, BR, Yang, S-H, Johnson, Z, Lorthongpanich, C, Kuo, HC, Parnpai, R & Chan, AWS 2010, 'Monkey hybrid stem cells develop cellular features of Huntington's disease', BMC Cell Biology, vol. 11, 12. https://doi.org/10.1186/1471-2121-11-12

Monkey hybrid stem cells develop cellular features of Huntington's disease. / Laowtammathron, Chuti; Cheng, Eric C.H.; Cheng, Pei Hsun; Snyder, Brooke R.; Yang, Shang-Hsun; Johnson, Zach; Lorthongpanich, Chanchao; Kuo, Hung Chih; Parnpai, Rangsun; Chan, Anthony W.S.

In: BMC Cell Biology, Vol. 11, 12, 05.02.2010.

Research output: Contribution to journalArticle

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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.

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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