Comparison of the calcium signaling alterations in GABA-ergic medium spiny neurons produced from iPSCs of different origins

Disease models based on induced pluripotent stem cells (iPSCs) are in high demand because of their physiological adequacy and well-reproducibility of the pathological phenotype. Nowadays, the most common approach to generate iPSCs is the reprogramming of somatic cells using vectors based on lentivir...

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Published in:	Biochimie Vol. 222; pp. 63 - 71
Main Authors:	Oshkolova, Arina A., Grekhnev, Dmitriy A., Kruchinina, Anna A., Belikova, Lilia D., Volovikov, Egor A., Lebedeva, Olga S., Bogomazova, Alexandra N., Vigont, Vladimir A., Lagarkova, Maria A., Kaznacheyeva, Elena V.
Format:	Journal Article
Language:	English
Published:	France Elsevier B.V 01-07-2024
Subjects:	Calcium - metabolism Calcium Signaling Cell Differentiation Cells, Cultured Fibroblasts - cytology Fibroblasts - metabolism Fluorescent calcium imaging GABAergic Neurons - cytology GABAergic Neurons - metabolism Humans Huntington's disease Induced pluripotent stem cells Induced Pluripotent Stem Cells - cytology Induced Pluripotent Stem Cells - metabolism Integrative reprogramming methods Lentivirus - genetics Medium Spiny Neurons Neurons - cytology Neurons - metabolism Non-integrative reprogramming methods Sendai virus Store-operated calcium entry Voltage-gated calcium entry Calcium signaling Induced pluripotent stem cells Store-operated calcium entry Non-integrative reprogramming methods Fluorescent calcium imaging Integrative reprogramming methods Huntington's disease Voltage-gated calcium entry
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Summary:	Disease models based on induced pluripotent stem cells (iPSCs) are in high demand because of their physiological adequacy and well-reproducibility of the pathological phenotype. Nowadays, the most common approach to generate iPSCs is the reprogramming of somatic cells using vectors based on lentivirus or Sendai virus. We have previously shown impairments of calcium signaling including store-operated calcium entry in Huntington's disease-specific iPSCs-based GABA-ergic medium spiny neurons. However, different approaches for iPSCs generation make it difficult to compare the models since the mechanism of reprogramming may influence the electrophysiological properties of the terminally differentiated neurons. Here, we have studied the features of calcium homeostasis in GABA-ergic medium spiny neurons differentiated from iPSCs obtained from fibroblasts of the same donor using different methods. Our data demonstrated that there were no significant differences neither in calcium influx through the store-operated channels, nor in the levels of proteins activating this type of calcium entry in neurons differentiated from iPSCs generated with lenti- and Sendai viruses-based approaches. We also found no differences in voltage-gated calcium entry for these neurons. Thus, we clearly showed that various methods of cell reprogramming result in similar deregulations in neuronal calcium signaling which substantiates the ability to combine the experimental data on functional studies of ion channels in models based on iPSCs obtained by different methods and expands the prospects for the use of biobanking. •Different methods of iPSCs generation result in similar neuronal calcium signaling.•Data obtained with different iPSCs-based models can be combined.•Calcium alterations in HD-specific neurons do not depend on iPSCs generation method.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0300-9084 1638-6183
DOI:	10.1016/j.biochi.2023.12.011