scholarly journals Molecular and electrophysiological features of spinocerebellar ataxia type seven in induced pluripotent stem cells

2018 ◽  
Author(s):  
RJ Burman ◽  
LM Watson ◽  
DC Smith ◽  
JV Raimondo ◽  
R Ballo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
Induced Pluripotent Stem Cells ◽  
Spinocerebellar Ataxia ◽  
Pluripotent Stem Cells ◽  
Spinocerebellar Ataxia Type ◽  
Patient Specific ◽  
Retinal Photoreceptors ◽  
Spinocerebellar Ataxia Type 7 ◽  
Induced Pluripotent

AbstractSpinocerebellar 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 demonstrate that iPSC-derived neurons and photoreceptors from SCA7 patients express molecular and electrophysiological differences that are 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.

scholarly journals Molecular and electrophysiological features of spinocerebellar ataxia type seven in induced pluripotent stem cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247434
Author(s):  
Richard J. Burman ◽  
Lauren M. Watson ◽  
Danielle C. Smith ◽  
Joseph V. Raimondo ◽  
Robea Ballo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
Induced Pluripotent Stem Cells ◽  
Spinocerebellar Ataxia ◽  
Pluripotent Stem Cells ◽  
Spinocerebellar Ataxia Type ◽  
Patient Specific ◽  
Retinal Photoreceptors ◽  
Spinocerebellar Ataxia Type 7 ◽  
Induced Pluripotent

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.

scholarly journals Generation of Human-Induced Pluripotent Stem Cells to Model Spinocerebellar Ataxia Type 2 In vitro

2012 ◽  
Vol 51 (2) ◽  
pp. 237-248 ◽  
Author(s):  
Guangbin Xia ◽  
Katherine Santostefano ◽  
Takashi Hamazaki ◽  
Jilin Liu ◽  
S. H. Subramony ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Spinocerebellar Ataxia ◽  
Pluripotent Stem Cells ◽  
Spinocerebellar Ataxia Type ◽  
Spinocerebellar Ataxia Type 2 ◽  
Induced Pluripotent

scholarly journals Applications of Induced Pluripotent Stem Cells in Studying the Neurodegenerative Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Wenbin Wan ◽  
Lan Cao ◽  
Bill Kalionis ◽  
Shijin Xia ◽  
Xiantao Tai
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Neurodegenerative Disorders ◽  
Embryonic Stem ◽  
Patient Specific ◽  
Disease Models ◽  
Species Variation ◽  
Induced Pluripotent

Neurodegeneration is the umbrella term for the progressive loss of structure or function of neurons. Incurable neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) show dramatic rising trends particularly in the advanced age groups. However, the underlying mechanisms are not yet fully elucidated, and to date there are no biomarkers for early detection or effective treatments for the underlying causes of these diseases. Furthermore, due to species variation and differences between animal models (e.g., mouse transgenic and knockout models) of neurodegenerative diseases, substantial debate focuses on whether animal and cell culture disease models can correctly model the condition in human patients. In 2006, Yamanaka of Kyoto University first demonstrated a novel approach for the preparation of induced pluripotent stem cells (iPSCs), which displayed similar pluripotency potential to embryonic stem cells (ESCs). Currently, iPSCs studies are permeating many sectors of disease research. Patient sample-derived iPSCs can be used to construct patient-specific disease models to elucidate the pathogenic mechanisms of disease development and to test new therapeutic strategies. Accordingly, the present review will focus on recent progress in iPSC research in the modeling of neurodegenerative disorders and in the development of novel therapeutic options.

scholarly journals Utilising Induced Pluripotent Stem Cells in Neurodegenerative Disease Research: Focus on Glia

2021 ◽  
Vol 22 (9) ◽  
pp. 4334
Author(s):  
Katrina Albert ◽  
Jonna Niskanen ◽  
Sara Kälvälä ◽  
Šárka Lehtonen
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Induced Pluripotent Stem Cells ◽  
Glial Cells ◽  
Pluripotent Stem Cells ◽  
Cell Types ◽  
Human Ipscs ◽  
Induced Pluripotent

Induced pluripotent stem cells (iPSCs) are a self-renewable pool of cells derived from an organism’s somatic cells. These can then be programmed to other cell types, including neurons. Use of iPSCs in research has been two-fold as they have been used for human disease modelling as well as for the possibility to generate new therapies. Particularly in complex human diseases, such as neurodegenerative diseases, iPSCs can give advantages over traditional animal models in that they more accurately represent the human genome. Additionally, patient-derived cells can be modified using gene editing technology and further transplanted to the brain. Glial cells have recently become important avenues of research in the field of neurodegenerative diseases, for example, in Alzheimer’s disease and Parkinson’s disease. This review focuses on using glial cells (astrocytes, microglia, and oligodendrocytes) derived from human iPSCs in order to give a better understanding of how these cells contribute to neurodegenerative disease pathology. Using glia iPSCs in in vitro cell culture, cerebral organoids, and intracranial transplantation may give us future insight into both more accurate models and disease-modifying therapies.

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