scholarly journals Cellular stress responses of long-lived and cancer-resistant naked mole-rats

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Perinur Bozaykut
Keyword(s):  
Stress Responses ◽  
Pluripotent Stem Cells ◽  
Target Gene ◽  
Cellular Mechanisms ◽  
Cellular Defense ◽  
Cellular Stress Responses ◽  
Mouse Cells ◽  
Cellular Stresses ◽  
Induced Pluripotent ◽  
Transcription Factor Nuclear Factor

Abstract Objectives Some organisms are long-lived and naturally resistant to cancer such as naked mole-rats (NMRs). Studies have shown that these animals can better tolerate stress due to mechanisms, such as upregulation of antioxidant pathways and improved proteostasis. In the present study, we aimed to analyze the tolerance against stress and the cellular mechanisms related to the stress response in NMR cells comparative to mouse cells. Materials and methods NMR and mouse fibroblasts were exposed to cellular stresses including H2O2 and/or NaNO3 and the viability of the cells were analyzed. In addition messanger RNA (mRNA) expression of antioxidant transcription factor Nuclear factor erythroid-derived 2-like 2 (Nrf2) and its target gene NAD(P)H quinone dehydrogenase 1 (NQO1) were determined by qRT-PCR and comprehensive analysis of stress-related gene expression was performed by RNA-Sequencing in fibroblasts and induced pluripotent stem cells (iPSC). Results Surprisingly, NMR fibroblasts were found to be more sensitive than mouse cells to H2O2 and NaNO3. Furthermore, it was shown that fibroblasts and iPSCs mainly aren’t identical in the expression pattern of cellular defense signaling and several factors are mainly downregulated in NMR iPSCs. Conclusions Collectively, the data gained from the present study help to improve the understanding of evolved mechanisms that contribute to stress resistance, aging and cancer.

scholarly journals Versatility of Induced Pluripotent Stem Cells (iPSCs) for Improving the Knowledge on Musculoskeletal Diseases

2020 ◽  
Vol 21 (17) ◽  
pp. 6124
Author(s):  
Clara Sanjurjo-Rodríguez ◽  
Rocío Castro-Viñuelas ◽  
María Piñeiro-Ramil ◽  
Silvia Rodríguez-Fernández ◽  
Isaac Fuentes-Boquete ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Musculoskeletal Diseases ◽  
The Body ◽  
Cellular Mechanisms ◽  
Induced Pluripotent ◽  
New Strategies

Induced pluripotent stem cells (iPSCs) represent an unlimited source of pluripotent cells capable of differentiating into any cell type of the body. Several studies have demonstrated the valuable use of iPSCs as a tool for studying the molecular and cellular mechanisms underlying disorders affecting bone, cartilage and muscle, as well as their potential for tissue repair. Musculoskeletal diseases are one of the major causes of disability worldwide and impose an important socio-economic burden. To date there is neither cure nor proven approach for effectively treating most of these conditions and therefore new strategies involving the use of cells have been increasingly investigated in the recent years. Nevertheless, some limitations related to the safety and differentiation protocols among others remain, which humpers the translational application of these strategies. Nonetheless, the potential is indisputable and iPSCs are likely to be a source of different types of cells useful in the musculoskeletal field, for either disease modeling or regenerative medicine. In this review, we aim to illustrate the great potential of iPSCs by summarizing and discussing the in vitro tissue regeneration preclinical studies that have been carried out in the musculoskeletal field by using iPSCs.

scholarly journals Dysregulation of neuron differentiation in an autistic savant with exceptional memory

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Jinjing Song ◽  
Xiujuan Yang ◽  
Ying Zhou ◽  
Lei Chen ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Pluripotent Stem Cells ◽  
Neurodevelopmental Disorders ◽  
Autism Spectrum ◽  
Learning Difficulty ◽  
Spine Density ◽  
Single Patient ◽  
Cellular Mechanisms ◽  
Savant Syndrome ◽  
Induced Pluripotent ◽  
Underlying Pathogenesis

Abstract Autism spectrum disorder (ASD) is a heterogeneous group of complex neurodevelopmental disorders without a unique or definite underlying pathogenesis. Although savant syndrome is common in ASD, few models are available for studying the molecular and cellular mechanisms of this syndrome. In this study, we generated urinary induced pluripotent stem cells (UiPSCs) from a 13-year-old male autistic savant with exceptional memory. The UiPSC-derived neurons of the autistic savant exhibited upregulated expression levels of ASD genes/learning difficulty-related genes, namely PAX6, TBR1 and FOXP2, accompanied by hypertrophic neural somas, enlarged spines, reduced spine density, and an increased frequency of spontaneous excitatory postsynaptic currents. Although this study involved only a single patient and a single control because of the rarity of such cases, it provides the first autistic savant UiPSC model that elucidates the potential cellular mechanisms underlying the condition.

In vitro pathological modelling using patient-specific induced pluripotent stem cells: the case of progeria

2011 ◽  
Vol 39 (6) ◽  
pp. 1775-1779 ◽  
Author(s):  
Xavier Nissan ◽  
Sophie Blondel ◽  
Marc Peschanski
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Systemic Disease ◽  
Accelerated Aging ◽  
Cell Types ◽  
Patient Specific ◽  
Cellular Mechanisms ◽  
Induced Pluripotent

Progeria, also known as HGPS (Hutchinson–Gilford progeria syndrome), is a rare fatal genetic disease characterized by an appearance of accelerated aging in children. This syndrome is typically caused by mutations in codon 608 (C1804T) of the gene encoding lamins A and C, LMNA, leading to the production of a truncated form of the protein called progerin. Owing to their unique potential to self-renew and to differentiate into any cell types of the organism, pluripotent stem cells offer a unique tool to study molecular and cellular mechanisms related to this global and systemic disease. Recent studies have exploited this potential by generating human induced pluripotent stem cells from HGPS patients' fibroblasts displaying several phenotypic defects characteristic of HGPS such as nuclear abnormalities, progerin expression, altered DNA-repair mechanisms and premature senescence. Altogether, these findings provide new insights on the use of pluripotent stem cells for pathological modelling and may open original therapeutic perspectives for diseases that lack pre-clinical in vitro human models, such as HGPS.

scholarly journals Human iPSC-Based Model Reveals NOX4 as Therapeutic Target in Duchenne Cardiomyopathy

2021 ◽  
Author(s):  
Robin Duelen ◽  
Domiziana Costamagna ◽  
Guillaume Gilbert ◽  
Liesbeth De Waele ◽  
Nathalie Goemans ◽  
...  
Keyword(s):  
Stress Responses ◽  
Early Death ◽  
Dystrophin Gene ◽  
Patient Specific ◽  
Ros Production ◽  
Atp Production ◽  
Protein Levels ◽  
Nadph Oxidase 4 ◽  
Cellular Stress Responses ◽  
Induced Pluripotent

Duchenne muscular dystrophy (DMD) is an X-linked progressive muscle disorder, caused by mutations in the Dystrophin gene. Cardiomyopathy is one of the major causes of early death. In this study, we used DMD patient-specific induced pluripotent stem cells (iPSCs) to model cardiomyopathic features in DMD and unravel novel pathological mechanistic insights. Cardiomyocytes (CMs) differentiated from DMD iPSCs showed enhanced premature cell death, due to significantly elevated intracellular reactive oxygen species (ROS) concentrations, as a result of depolarized mitochondria and high NADPH oxidase 4 (NOX4) protein levels. Genetic correction of Dystrophin through CRISPR/Cas9 editing restored normal ROS levels. Application of ROS reduction by N-acetyl-L-cysteine (NAC), partial Dystrophin re-expression by ataluren (PTC124) and enhancing mitochondrial electron transport chain function by idebenone improved cell survival of DMD iPSC-CMs. We show applications that could counteract the detrimental oxidative stress environment in DMD iPSC-CMs by stimulating adenosine triphosphate (ATP) production. ATP could bind to the ATP-binding domain in the NOX4 enzyme, and we demonstrate that ATP resulted in partial inhibition of the NADPH-dependent ROS production of NOX4. Considering the complexity and the early cellular stress responses in DMD cardiomyopathy, we propose to target ROS production and prevent the detrimental effects of NOX4 on DMD CMs as a promising therapeutic strategy.

Directed differentiation of mouse-induced pluripotent stem cells generates dopaminergic nerve

2010 ◽  
Vol 34 (8) ◽  
pp. S36-S36
Author(s):  
Ping Duan ◽  
Xuelin Ren ◽  
Wenhai Yan ◽  
Xuefei Han ◽  
Xu Yan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Directed Differentiation ◽  
Induced Pluripotent
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