Multiomic analysis on human cell model of wolfram syndrome reveals changes in mitochondrial morphology and function
| العنوان: | Multiomic analysis on human cell model of wolfram syndrome reveals changes in mitochondrial morphology and function |
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| المؤلفون: | Magdalena Lebiedzinska-Arciszewska, Bartlomiej Pawlik, Piotr Rieske, Joanna Taha, Wojciech Fendler, Hanna Nieznanska, Miljan Kuljanin, Aneta Wlodarczyk, Dominika Michałek, Agnieszka Zmysłowska, Beata Małachowska, Joseph D. Mancias, Wojciech Młynarski, Marcin Stanczak, Maciej Borowiec, Mariusz R. Wieckowski, Dagmara Grot |
| المصدر: | Cell Communication and Signaling, Vol 19, Iss 1, Pp 1-14 (2021) Cell Communication and Signaling : CCS |
| بيانات النشر: | BMC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Proteomics, Wolfram syndrome, Respiratory chain, Biology, Mitochondrion, Biochemistry, Transcriptome, chemistry.chemical_compound, medicine, Induced pluripotent stem cell, Transcriptomics, Molecular Biology, QH573-671, Research, Cell Biology, Tunicamycin, medicine.disease, Neural stem cell, Cell biology, Mitochondria, chemistry, nervous system, Unfolded protein response, Medicine, ER stress, Cytology |
| الوصف: | Background Wolfram syndrome (WFS) is a rare autosomal recessive syndrome in which diabetes mellitus and neurodegenerative disorders occur as a result of Wolframin deficiency and increased ER stress. In addition, WFS1 deficiency leads to calcium homeostasis disturbances and can change mitochondrial dynamics. The aim of this study was to evaluate protein levels and changes in gene transcription on human WFS cell model under experimental ER stress. Methods We performed transcriptomic and proteomic analysis on WFS human cell model—skin fibroblasts reprogrammed into induced pluripotent stem (iPS) cells and then into neural stem cells (NSC) with subsequent ER stress induction using tunicamycin (TM). Results were cross-referenced with publicly available RNA sequencing data in hippocampi and hypothalami of mice with WFS1 deficiency. Results Proteomic analysis identified specific signal pathways that differ in NSC WFS cells from healthy ones. Next, detailed analysis of the proteins involved in the mitochondrial function showed the down-regulation of subunits of the respiratory chain complexes in NSC WFS cells, as well as the up-regulation of proteins involved in Krebs cycle and glycolysis when compared to the control cells. Based on pathway enrichment analysis we concluded that in samples from mice hippocampi the mitochondrial protein import machinery and OXPHOS were significantly down-regulated. Conclusions Our results show the functional and morphological secondary mitochondrial damage in patients with WFS. Graphical Abstract |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::79d969bef511c2898189cf414590f38a https://doaj.org/article/e9ae24e4ded347729d7a31887a6ccfdf |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....79d969bef511c2898189cf414590f38a |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |