Bui Hien, Andersson Simon, Sola-Carvajal Agustin, De Marchi Tommaso, Vähäkangas Eliisa, Holopainen Minna, House Andrew H, Rovenko Bohdana M, Englund Johanna I, Kasper Maria, Kuuluvainen Emilia, Käkelä Reijo, Hietakangas Ville, Niméus Emma, Katajisto Pekka
Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, 00790, Helsinki, Finland.
Institute of Biotechnology, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, 00790, Helsinki, Finland.
Nat Commun. 2025 Apr 26;16(1):3932. doi: 10.1038/s41467-025-58752-z.
Selective inheritance of sub-cellular components has emerged as a mechanism guiding stem cell fate after asymmetric cell divisions. Peroxisomes play a crucial role in multiple metabolic processes such as fatty acid metabolism and reactive oxygen species detoxification, but the apportioning of peroxisomes during stem cell division remains understudied. Here, we develop a mouse model and labeling technique to follow the dynamics of distinct peroxisome age-classes, and find that old peroxisomes are inherited by the daughter cell retaining full stem cell potency in mammary and epidermal stem cell divisions. Old peroxisomes carry Glucose-6-phosphate-dehydrogenase, whose specific location on the peroxisomal membrane promotes stem cell function by facilitating peroxisomal ether lipid synthesis. Our study demonstrates age-selective apportioning of peroxisomes in vivo, and unveils how functional heterogeneity of peroxisomes is utilized by asymmetrically dividing cells to metabolically divert the fate of the two daughter cells.
亚细胞成分的选择性遗传已成为不对称细胞分裂后指导干细胞命运的一种机制。过氧化物酶体在脂肪酸代谢和活性氧解毒等多种代谢过程中发挥着关键作用，但干细胞分裂过程中过氧化物酶体的分配仍未得到充分研究。在这里，我们开发了一种小鼠模型和标记技术来追踪不同年龄阶段过氧化物酶体的动态变化，并发现旧的过氧化物酶体由在乳腺和表皮干细胞分裂中保留完全干细胞潜能的子细胞继承。旧的过氧化物酶体携带葡萄糖-6-磷酸脱氢酶，其在过氧化物酶体膜上的特定位置通过促进过氧化物酶体醚脂合成来促进干细胞功能。我们的研究证明了过氧化物酶体在体内的年龄选择性分配，并揭示了不对称分裂细胞如何利用过氧化物酶体的功能异质性在代谢上改变两个子细胞的命运。
