In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 2 ( 2021-2-24), p. e0247434-
Kurzfassung:
Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disease caused by a polyglutamine repeat expansion in the ATXN7 gene. Patients with this disease suffer from a degeneration of their cerebellar Purkinje neurons and retinal photoreceptors that result in a progressive ataxia and loss of vision. As with many neurodegenerative diseases, studies of pathogenesis have been hindered by a lack of disease-relevant models. To this end, we have generated induced pluripotent stem cells (iPSCs) from a cohort of SCA7 patients in South Africa. First, we differentiated the SCA7 affected iPSCs into neurons which showed evidence of a transcriptional phenotype affecting components of STAGA ( ATXN7 and KAT2A ) and the heat shock protein pathway ( DNAJA1 and HSP70 ). We then performed electrophysiology on the SCA7 iPSC-derived neurons and found that these cells show features of functional aberrations. Lastly, we were able to differentiate the SCA7 iPSCs into retinal photoreceptors that also showed similar transcriptional aberrations to the SCA7 neurons. Our findings give technical insights on how iPSC-derived neurons and photoreceptors can be derived from SCA7 patients and demonstrate that these cells express molecular and electrophysiological differences that may be indicative of impaired neuronal health. We hope that these findings will contribute towards the ongoing efforts to establish the cell-derived models of neurodegenerative diseases that are needed to develop patient-specific treatments.
Materialart:
Online-Ressource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0247434
DOI:
10.1371/journal.pone.0247434.g001
DOI:
10.1371/journal.pone.0247434.g002
DOI:
10.1371/journal.pone.0247434.g003
DOI:
10.1371/journal.pone.0247434.g004
DOI:
10.1371/journal.pone.0247434.s001
DOI:
10.1371/journal.pone.0247434.s002
DOI:
10.1371/journal.pone.0247434.s003
DOI:
10.1371/journal.pone.0247434.s004
DOI:
10.1371/journal.pone.0247434.s005
DOI:
10.1371/journal.pone.0247434.s006
DOI:
10.1371/journal.pone.0247434.s007
DOI:
10.1371/journal.pone.0247434.s008
DOI:
10.1371/journal.pone.0247434.s009
DOI:
10.1371/journal.pone.0247434.s010
DOI:
10.1371/journal.pone.0247434.s011
DOI:
10.1371/journal.pone.0247434.r001
DOI:
10.1371/journal.pone.0247434.r002
DOI:
10.1371/journal.pone.0247434.r003
DOI:
10.1371/journal.pone.0247434.r004
DOI:
10.1371/journal.pone.0247434.r005
DOI:
10.1371/journal.pone.0247434.r006
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2021
ZDB Id:
2267670-3
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