Limited oxygen availability in standard cell culture alters metabolism and function in terminally-differentiated cells
Limited oxygen availability in standard cell culture alters metabolism and function in terminally-differentiated cells
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标准细胞培养物中有限的氧气供应改变了终末分化细胞的代谢和功能
DOI：
10.1101/2022.11.29.516437
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Tan J
中科院分区：
文献类型：
--
作者：
Tan J
细胞培养是生物医学研究的主力，通常被认为是高氧的。然而，细胞的耗氧量却被低估了。高细胞呼吸速率会迅速耗尽氧气，导致局部缺氧。细胞周氧水平的增加重新连接了单层和类器官培养中多种有丝分裂后细胞系的代谢。在标准条件下，培养的脂肪细胞处于缺氧且高度糖酵解的状态。氧气利用率的增加将葡萄糖流向线粒体，并增加了葡萄糖衍生碳的脂肪生成。这些代谢变化与数千个基因表达变化相结合，使脂肪细胞对胰岛素和脂肪分解刺激更加敏感。重要的是，途径分析揭示了氧张力的增加使得体外脂肪细胞与体内脂肪组织更加相似。 hPSC 衍生的肝细胞和心脏类器官的功能也因氧气增加而增强。我们的研究结果表明，氧气在许多标准细胞培养系统中受到限制，并强调了控制氧气可用性如何提高细胞模型的可翻译性。
Cell culture, the workhorse of biomedical research, is generally considered to be hyperoxic. However, oxygen consumption by cells is underappreciated. High cellular respiration rates can rapidly deplete oxygen, resulting in local hypoxia. Increasing pericellular oxygen levels rewired the metabolism of multiple post-mitotic cell-lines, both in monolayer and organoid culture. Under standard conditions, cultured adipocytes are hypoxic and highly glycolytic. Increased oxygen availability diverted glucose flux toward mitochondria and increased lipogenesis from glucose-derived carbon. These metabolic changes were coupled to thousands of gene expression changes, and rendered adipocytes more sensitive to insulin and lipolytic stimuli. Importantly, pathway analyses revealed increasing oxygen tension madein vitroadipocytes more similar toin vivoadipose tissue. hPSC-derived hepatocytes and cardiac organoids were also functionally enhanced by increased oxygen. Our findings suggest that oxygen is limiting in many standard cell culture systems, and highlight how controlling oxygen availability can improve translatability of cell models.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
13.8
作者：
Liberti MV;Locasale JW
通讯作者：
Locasale JW
DOI：
10.1101/2020.06.08.140558
发表时间：
2020-06
期刊：
bioRxiv
影响因子：
--
作者：
Alba Luengo;Zhaoqi Li;D. Y. Gui;Lucas B. Sullivan;Maria Zagorulya;Brian T. Do;R. Ferreira;Adi Naamati;A. Ali;C. Lewis;Craig J. Thomas;S. Spranger;N. Matheson;M. V. Vander Heiden
通讯作者：
Alba Luengo;Zhaoqi Li;D. Y. Gui;Lucas B. Sullivan;Maria Zagorulya;Brian T. Do;R. Ferreira;Adi Naamati;A. Ali;C. Lewis;Craig J. Thomas;S. Spranger;N. Matheson;M. V. Vander Heiden
影响因子：
3.8
作者：
Sucosky, P;Osorio, DF;Neitzel, GP
通讯作者：
Neitzel, GP
影响因子：
5.1
作者：
Gilglioni EH;Chang JC;Duijst S;Go S;Adam AAA;Hoekstra R;Verhoeven AJ;Ishii-Iwamoto EL;Oude Elferink RPJ
通讯作者：
Oude Elferink RPJ