Expansion of induced pluripotent stem cells under consideration of bioengineering aspects: part 2

Applied Microbiology and Biotechnology, Год журнала: 2025, Номер 109(1)

Опубликована: Фев. 6, 2025

Язык: Английский

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Trajectory analysis of hepatic stellate cell differentiation reveals metabolic regulation of cell commitment and fibrosis

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 10, 2025

Defining the trajectory of cells during differentiation and disease is key for uncovering mechanisms driving cell fate identity. However, trajectories human remain largely unexplored due to challenges studying them with samples. In this study, we investigate proteome iPSCs hepatic stellate (diHSCs) identify RORA as a transcription factor governing metabolic reprogramming HSCs necessary diHSCs' commitment, identity, activation. Using deficient pharmacologic interventions, show that required early prevents diHSCs activation by reducing high energetic state cells. While knockout mice have enhanced fibrosis, agonists rescue multi-organ fibrosis in vivo models. Notably, expression correlates negatively liver markers patients disease. This study reveals regulates plasticity, important mesoderm differentiation, pericyte quiescence, influencing commitment Here, authors differentiating into governs essential quiescent phenotype.

Язык: Английский

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Cell energy metabolism and bone formation

Bone Reports, Год журнала: 2022, Номер 16, С. 101594 - 101594

Опубликована: Май 27, 2022

Energy metabolism plays an important role in cell and tissue ability to effectively function, maintain homeostasis, perform repair. Yet, the of energy skeletal tissues general bone, particular, remains understudied. We, here, review aspects relevant bone tissue, such as: i) availability substrates oxygen; ii) regulatory mechanisms most active e.g. HIF BMP; iii) crosstalk bioenergetics with other functions, proliferation differentiation; iv) glycolysis mitochondrial oxidative phosphorylation osteogenic lineage; v) significant changes observed aging pathologies. In addition, we available methods study on a subcellular, cellular, live animal levels.

Язык: Английский

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Control of cell metabolism by the epidermal growth factor receptor

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Год журнала: 2022, Номер 1869(12), С. 119359 - 119359

Опубликована: Сен. 9, 2022

Язык: Английский

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Oxidative phosphorylation in bone cells

Bone Reports, Год журнала: 2023, Номер 18, С. 101688 - 101688

Опубликована: Май 23, 2023

The role of energy metabolism in bone cells is an active field investigation. Bone are metabolically very and require high levels the form adenosine triphosphate (ATP) to support their function. ATP generated cytosol via glycolysis coupled with lactic acid fermentation mitochondria oxidative phosphorylation (OXPHOS). OXPHOS final convergent metabolic pathway for all steps dietary nutrients catabolism. formation driven by electrochemical gradient that forms across mitochondrial inner membrane through activity electron transport chain (ETC) complexes requires presence oxygen as acceptor. current literature supports a model which main source undifferentiated mesenchymal progenitors terminally differentiated osteoblasts, whereas appears relevant intermediate stage differentiation those cells. Conversely, osteoclasts progressively increase during until they become multinucleated mitochondrial-rich terminal Despite abundance mitochondria, mature considered ATP-depleted, availability critical factor regulates low survival capacity these cells, rapidly undergo death apoptosis. In addition ATP, bioenergetic generates reactive species (ROS) metabolites regulate variety cellular functions, including epigenetics changes genomic DNA histones. This review will briefly discuss cross-talks OXPHOS-glycolysis process

Язык: Английский

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Mitochondrial metabolism in neural stem cells and implications for neurodevelopmental and neurodegenerative diseases

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Март 4, 2024

Abstract Mitochondria are cytoplasmic organelles having a fundamental role in the regulation of neural stem cell (NSC) fate during development and maintenance. During embryonic adult neurogenesis, NSCs undergo metabolic switch from glycolytic to oxidative phosphorylation with rise mitochondrial DNA (mtDNA) content, changes mitochondria shape size, physiological augmentation reactive oxygen species which together drive proliferate differentiate. Genetic epigenetic modifications proteins involved cellular differentiation (Mechanistic Target Rapamycin), proliferation (Wingless-type), hypoxia (Mitogen-activated protein kinase)–and all connected by common key regulatory factor Hypoxia Inducible Factor-1A–are deemed be responsible for shift and, consequently, NSC pathological conditions. Both primary dysfunction due mutations nuclear or mtDNA secondary (OXPHOS) metabolism, dynamics, organelle interplay pathways can contribute neurodevelopmental progressive neurodegenerative disorders. This review analyses physiology pathology starting available vitro vivo models highlights current knowledge concerning this process.

Язык: Английский

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Taurine rescues mitochondria-related metabolic impairments in the patient-derived induced pluripotent stem cells and epithelial-mesenchymal transition in the retinal pigment epithelium

Redox Biology, Год журнала: 2021, Номер 41, С. 101921 - 101921

Опубликована: Фев. 28, 2021

Mitochondria participate in various metabolic pathways, and their dysregulation results multiple disorders, including aging-related diseases. However, the changes mechanisms of mitochondrial disorders are not fully understood. Here, we found that induced pluripotent stem cells (iPSCs) from a patient with myopathy, encephalopathy, lactic acidosis, stroke-like episodes (MELAS) showed attenuated proliferation survival when glycolysis was inhibited. These deficits were rescued by taurine administration. Metabolomic analyses ratio reduced (GSH) to oxidized glutathione (GSSG) decreased; whereas levels cysteine, substrate GSH, oxidative stress markers upregulated MELAS iPSCs. Taurine normalized these changes, suggesting iPSCs affected its influence. We also analyzed retinal pigment epithelium (RPE) differentiated using three-dimensional culture system it epithelial mesenchymal transition (EMT), which suppressed taurine. Therefore, dysfunction caused accumulation depleted EMT RPE could be involved pathogenesis. Because all phenomena sensitive treatment, conclude administration may potential new therapeutic approach for mitochondria-related

Язык: Английский

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Cultivation of Cells in a Physiological Plasmax Medium Increases Mitochondrial Respiratory Capacity and Reduces Replication Levels of RNA Viruses

Antioxidants, Год журнала: 2021, Номер 11(1), С. 97 - 97

Опубликована: Дек. 30, 2021

Changes in metabolic pathways are often associated with the development of various pathologies including cancer, inflammatory diseases, obesity and syndrome. Identification particular events that dysregulated may yield strategies for pharmacologic intervention. However, such studies hampered by use classic cell media do not reflect metabolite composition exists blood plasma which cause non-physiological adaptations cultured cells. In recent years two groups presented aim to human plasma, namely plasma-like medium (HPLM) Plasmax. Here we describe that, four different mammalian lines, Plasmax enhances mitochondrial respiration. This is formation vast networks enhanced production reactive oxygen species (ROS). Interestingly, cells cultivated displayed significantly less lysosomes than when any standard were used. Finally, support replication RNA viruses, as hepatitis C virus (HCV) influenza A (IAV), severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) several others, albeit at lower levels delayed kinetics. conclusion, metabolism context viral infections, especially those concerning mitochondria, lysosomes, or redox systems, should be performed medium.

Язык: Английский

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Ciliary neurotrophic factor-mediated neuroprotection involves enhanced glycolysis and anabolism in degenerating mouse retinas

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Ноя. 17, 2022

Abstract Ciliary neurotrophic factor (CNTF) acts as a potent neuroprotective cytokine in multiple models of retinal degeneration. To understand mechanisms underlying its broad effects, we have investigated the influence CNTF on metabolism mouse model photoreceptor treatment improves morphology mitochondria, but also leads to reduced oxygen consumption and suppressed respiratory chain activities. Molecular analyses show elevated glycolytic pathway gene transcripts active enzymes. Metabolomics detect significantly higher levels ATP energy currency phosphocreatine, metabolites, increased TCA cycle lipid biosynthetic intermediates, nucleotides, amino acids. Moreover, restores key antioxidant glutathione wild type level. Therefore, impacts metabolic status degenerating retinas by promoting aerobic glycolysis augmenting anabolic These findings reveal cellular enhanced neuronal viability suggest potential therapies for treating

Язык: Английский

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A regeneration-triggered metabolic adaptation is necessary for cell identity transitions and cell cycle re-entry to support blastema formation and bone regeneration

eLife, Год журнала: 2022, Номер 11

Опубликована: Авг. 15, 2022

Regeneration depends on the ability of mature cells at injury site to respond injury, generating tissue-specific progenitors that incorporate blastema and proliferate reconstitute original organ architecture. The metabolic microenvironment has been tightly connected cell function identity during development tumorigenesis. Yet, link between metabolism mechanistic level in a regenerative context remains unclear. adult zebrafish caudal fin, bone specifically, have crucial for understanding contribution tissue regeneration. Here, we use this model explore relevance glucose fate transitions preceding new osteoblast formation assembly. We show triggers modulation profile early stages regeneration enhance glycolysis expense mitochondrial oxidation. This adaptation mediates transcriptional changes make amenable be reprogramed into pre-osteoblasts induces cycle re-entry progression. Manipulation led severe reduction pre-osteoblast pool, diminishing their capacity generate osteoblasts, complete abrogation formation. Overall, our data indicate alterations powerful instructive role regulating genetic programs dictate decisions stimulate proliferation, thereby providing deeper mechanisms

Язык: Английский

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