دورية أكاديمية
A mitochondrial NADPH-cholesterol axis regulates extracellular vesicle biogenesis to support hematopoietic stem cell fate
| العنوان: | A mitochondrial NADPH-cholesterol axis regulates extracellular vesicle biogenesis to support hematopoietic stem cell fate |
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| المؤلفون: | Bonora, Massimo, Morganti, Claudia, van Gastel, Nick, Ito, Kyoko, Calura, Enrica, Zanolla, Ilaria, Ferroni, Letizia, Zhang, Yang, Jung, Yookyung, Sales, Gabriele, Martini, Paolo, Nakamura, Takahisa, Lasorsa, Francesco Massimo, Finkel, Toren, Lin, Charles P., Zavan, Barbara, Pinton, Paolo, Georgakoudi, Irene, Romualdi, Chiara, Scadden, David T., Ito, Keisuke |
| المساهمون: | UCL - SSS/DDUV/MEMI - Cellular Metabolism & Microenvironment |
| المصدر: | Cell Stem Cell, Vol. 31, no. 3, p. 359-377 (2024) |
| بيانات النشر: | Cell Press |
| سنة النشر: | 2024 |
| المجموعة: | DIAL@USL-B (Université Saint-Louis, Bruxelles) |
| الوصف: | Mitochondrial fatty acid oxidation (FAO) is essential for hematopoietic stem cell (HSC) self-renewal; however, the mechanism by which mitochondrial metabolism controls HSC fate remains unknown. Here, we show that within the hematopoietic lineage, HSCs have the largest mitochondrial NADPH pools, which are required for proper HSC cell fate and homeostasis. Bioinformatic analysis of the HSC transcriptome, biochemical assays, and genetic inactivation of FAO all indicate that FAO-generated NADPH fuels cholesterol synthesis in HSCs. Interference with FAO disturbs the segregation of mitochondrial NADPH toward corresponding daughter cells upon single HSC division. Importantly, we have found that the FAO-NADPH-cholesterol axis drives extracellular vesicle (EV) biogenesis and release in HSCs, while inhibition of EV signaling impairs HSC self-renewal. These data reveal the existence of a mitochondrial NADPH-cholesterol axis for EV biogenesis that is required for hematopoietic homeostasis and highlight the non-stochastic nature of HSC fate determination. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1934-5909 1875-9777 |
| العلاقة: | boreal:285589; http://hdl.handle.net/2078.1/285589Test; urn:ISSN:1934-5909; urn:EISSN:1875-9777 |
| الإتاحة: | http://hdl.handle.net/2078.1/285589Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.FF5C21AA |
| قاعدة البيانات: | BASE |
| تدمد: | 19345909 18759777 |
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