Induced pluripotent stem cell - derived neurons for the study of spinocerebellar ataxia type 3
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Induced pluripotent stem cell - derived neurons for the study of spinocerebellar ataxia type 3. / Hansen, Susanne Kofoed; Stummann, Tina C.; Madsen, Helena Borland; Hasholt, Lis Frydenreich; Tümer, Zeynep; Nielsen, Jørgen Erik; Rasmussen, Mikkel Aabech; Nielsen, Troels Tolstrup; Daechsel, Justus C. A.; Fog, Karina; Hyttel, Poul.
I: Stem Cell Research, Bind 17, Nr. 2, 09.2016, s. 306-317.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Induced pluripotent stem cell - derived neurons for the study of spinocerebellar ataxia type 3
AU - Hansen, Susanne Kofoed
AU - Stummann, Tina C.
AU - Madsen, Helena Borland
AU - Hasholt, Lis Frydenreich
AU - Tümer, Zeynep
AU - Nielsen, Jørgen Erik
AU - Rasmussen, Mikkel Aabech
AU - Nielsen, Troels Tolstrup
AU - Daechsel, Justus C. A.
AU - Fog, Karina
AU - Hyttel, Poul
PY - 2016/9
Y1 - 2016/9
N2 - The neurodegenerative disease spinocerebellar ataxia type 3 (SCA3) is caused by a CAG-repeat expansion in the ATXN3 gene. In this study, induced pluripotent stem cell (iPSC) lines were established from two SCA3 patients. Dermal fibroblasts were reprogrammed using an integration-free method and the resulting SCA3 iPSCs were differentiated into neurons. These neuronal lines harbored the disease causing mutation, expressed comparable levels of several neuronal markers and responded to the neurotransmitters, glutamate/glycine, GABA and acetylcholine. Additionally, all neuronal cultures formed networks displaying synchronized spontaneous calcium oscillations within 28 days of maturation, and expressed the mature neuronal markers NeuN and Synapsin 1 implying a relatively advanced state of maturity, although not comparable to that of the adult human brain. Interestingly, we were not able to recapitulate the glutamate-induced ataxin-3 aggregation shown in a previously published iPSC-derived SCA3 model. In conclusion, we have generated a panel of SCA3 patient iPSCs and a robust protocol to derive neurons of relatively advanced maturity, which could potentially be valuable for the study of SCA3 disease mechanisms.
AB - The neurodegenerative disease spinocerebellar ataxia type 3 (SCA3) is caused by a CAG-repeat expansion in the ATXN3 gene. In this study, induced pluripotent stem cell (iPSC) lines were established from two SCA3 patients. Dermal fibroblasts were reprogrammed using an integration-free method and the resulting SCA3 iPSCs were differentiated into neurons. These neuronal lines harbored the disease causing mutation, expressed comparable levels of several neuronal markers and responded to the neurotransmitters, glutamate/glycine, GABA and acetylcholine. Additionally, all neuronal cultures formed networks displaying synchronized spontaneous calcium oscillations within 28 days of maturation, and expressed the mature neuronal markers NeuN and Synapsin 1 implying a relatively advanced state of maturity, although not comparable to that of the adult human brain. Interestingly, we were not able to recapitulate the glutamate-induced ataxin-3 aggregation shown in a previously published iPSC-derived SCA3 model. In conclusion, we have generated a panel of SCA3 patient iPSCs and a robust protocol to derive neurons of relatively advanced maturity, which could potentially be valuable for the study of SCA3 disease mechanisms.
U2 - 10.1016/j.scr.2016.07.004
DO - 10.1016/j.scr.2016.07.004
M3 - Journal article
C2 - 27596958
VL - 17
SP - 306
EP - 317
JO - Stem Cell Research
JF - Stem Cell Research
SN - 1873-5061
IS - 2
ER -
ID: 171655534