Glucose-6-phosphate-dehydrogenase on old peroxisomes maintains self-renewal of epithelial stem cells after asymmetric cell division
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.
Authors
- Pekka Katajisto (ORCID: https://orcid.org/0000-0002-3033-4189)
- Emilia Kuuluvainen (ORCID: https://orcid.org/0000-0003-0227-4331)
- Emma Niméus (ORCID: https://orcid.org/0000-0003-0262-9083)
- Simon Andersson (ORCID: https://orcid.org/0000-0002-2688-2318)
- Ville Hietakangas (ORCID: https://orcid.org/0000-0002-9900-7549)
- Maria Kasper (ORCID: https://orcid.org/0000-0002-6117-2717)
- Hien Bui
- Agustín Sola-Carvajal (ORCID: https://orcid.org/0000-0001-6568-0682)
- Minna Holopainen (ORCID: https://orcid.org/0000-0002-3030-8677)
- Johanna I. Englund (ORCID: https://orcid.org/0000-0001-9637-6843)
- Andrew H. House (ORCID: https://orcid.org/0000-0001-8705-0358)
- Bohdana M. Rovenko (ORCID: https://orcid.org/0000-0002-2512-7206)
- Tommaso De Marchi (ORCID: https://orcid.org/0000-0002-4845-1084)
- Eliisa Vähäkangas (ORCID: https://orcid.org/0000-0002-1649-2471)
- Reijo Käkelä (ORCID: https://orcid.org/0000-0003-4953-3062)
Institutions
- University of Helsinki (FI)
- Lund University (SE)
- Helsinki Institute of Physics (FI)
- Karolinska Institutet (SE)
- Biocenter Finland (FI)
- Skåne University Hospital (SE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-26
- DOI
- https://doi.org/10.1038/s41467-025-58752-z
- Citations
- 2
- Primary Topic
- Peroxisome Proliferator-Activated Receptors
- Type
- article
- Field-Weighted Citation Impact
- 1.61