线粒体
细胞命运测定
细胞生物学
生物
遗传(遗传算法)
细胞
遗传学
基因
转录因子
作者
Julia Döhla,Emilia Kuuluvainen,Nadja Gebert,Ana Luísa Amaral,Johanna Englund,Swetha Gopalakrishnan,Svetlana Konovalova,Anni I. Nieminen,Ella S Salminen,Rubén Torregrosa Muñumer,Kati J. Ahlqvist,Yang Yang,Hien Bui,Timo Otonkoski,Reijo Käkelä,Ville Hietakangas,Henna Tyynismaa,Alessandro Ori,Pekka Katajisto
标识
DOI:10.1038/s41556-021-00837-0
摘要
Metabolic characteristics of adult stem cells are distinct from their differentiated progeny, and cellular metabolism is emerging as a potential driver of cell fate conversions1-4. How these metabolic features are established remains unclear. Here we identified inherited metabolism imposed by functionally distinct mitochondrial age-classes as a fate determinant in asymmetric division of epithelial stem-like cells. While chronologically old mitochondria support oxidative respiration, the electron transport chain of new organelles is proteomically immature and they respire less. After cell division, selectively segregated mitochondrial age-classes elicit a metabolic bias in progeny cells, with oxidative energy metabolism promoting differentiation in cells that inherit old mitochondria. Cells that inherit newly synthesized mitochondria with low levels of Rieske iron-sulfur polypeptide 1 have a higher pentose phosphate pathway activity, which promotes de novo purine biosynthesis and redox balance, and is required to maintain stemness during early fate determination after division. Our results demonstrate that fate decisions are susceptible to intrinsic metabolic bias imposed by selectively inherited mitochondria.
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