Mitochondrial metabolism directs stemness and differentiation in P19 embryonal carcinoma stem cells
| Autor: | Ignacio Vega-Naredo, Inês A. Barbosa, Ludgero C. Tavares, Rui A. Carvalho, Paulo J. Oliveira, J R Erickson, Ana F. Branco, Jon M Holy, Rute Loureiro, Ed Perkins, Katia A. Mesquita |
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| Rok vydání: | 2014 |
| Předmět: |
Pluripotent Stem Cells
Teratocarcinoma Embryonal Carcinoma Stem Cells DNA Copy Number Variations Cell Survival Cellular differentiation Mitochondrion Biology Mice Adenosine Triphosphate Oxygen Consumption Spheroids Cellular Tumor Cells Cultured Animals Glycolysis Viability assay Molecular Biology Cell Proliferation Membrane Potential Mitochondrial Original Paper Dichloroacetic Acid Cell growth Cell Differentiation Cell Biology Mitochondria Cell biology Glucose Mitochondrial biogenesis Neoplastic Stem Cells Stem cell Energy Metabolism |
| Zdroj: | Cell Death & Differentiation. 21:1560-1574 |
| ISSN: | 1476-5403 1350-9047 |
| Popis: | The relationship between mitochondrial metabolism and cell viability and differentiation in stem cells (SCs) remains poorly understood. In the present study, we compared mitochondrial physiology and metabolism between P19SCs before/after differentiation and present a unique fingerprint of the association between mitochondrial activity, cell differentiation and stemness. In comparison with their differentiated counterparts, pluripotency of P19SCs was correlated with a strong glycolytic profile and decreased mitochondrial biogenesis and complexity: round, low-polarized and inactive mitochondria with a closed permeability transition pore. This decreased mitochondrial capacity increased their resistance against dichloroacetate. Thus, stimulation of mitochondrial function by growing P19SCs in glutamine/pyruvate-containing medium reduced their glycolytic phenotype, induced loss of pluripotent potential, compromised differentiation and became P19SCs sensitive to dichloroacetate. Because of the central role of this type of SCs in teratocarcinoma development, our findings highlight the importance of mitochondrial metabolism in stemness, proliferation, differentiation and chemoresistance. In addition, the present work suggests the regulation of mitochondrial metabolism as a tool for inducing cell differentiation in stem line therapies. |
| Databáze: | OpenAIRE |
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