The continuous functionality of our tissues is dependent on the presence of different cell types, which specialize in distinct activities. To keep the tissue healthy over time, specialized cells in most of our tissues are continuously renewed by the action of tissue stem cells. Some stem cells divide asymmetrically, producing two distinct daughter cells, one self-renewing stem cell and one specialized cell, in each division.
Self-renewing and specialized cells are known to have distinct metabolism that supports their specific functions. In a recent study, a research group from the University of Helsinki, led by Professor Pekka Katajisto, director of the Research Council of Finland funded Centre of Excellence in Stem Cell Metabolism, discovered that in mammalian asymmetrically dividing tissue stem cells, this cell fate decision can be guided by the age and metabolic status of peroxisomes.
“Peroxisomes are cell organelles that specialize in metabolic pathways such as reactive oxygen species (ROS) management and the production of certain lipids”, Katajisto explains.
The group has previously discovered that the maturation stage of another metabolic organelle, mitochondria, influences cell fate decisions in mammalian stem cells cultured in the laboratory.
“However, until now we did not know if the maturity of other organelles influences cell fate decisions and if this really takes place in tissues, or only in cells grown in the lab” Katajisto continues.
To answer these questions, Hien Bui, a PhD student in the Katajisto group, generated a mouse model where she could distinguish peroxisomes at different stages of their maturation in any given cell.
“We found that older peroxisomes promote renewal capacity of tissue stem cells both in the mammary gland and in the skin. This was surprising to us since when it comes to mitochondria, it’s the newer, less mature organelles that promote self-renewal. In the end we figured out that the maturation stage of the different organelles is set to match the metabolic needs of what that given cell will become” Bui explains.
In the study led by Bui, the group analyzed the protein content of the peroxisomes of different age and found that the localization of one metabolic enzyme specifically on the surface of old peroxisomes promotes self-renewal.
“We learned that by simply localizing certain metabolic reactions differently, cells can control whether they self-renew or differentiate” Katajisto summarizes.
Original article
Bui, H., Andersson, S., Sola-Carvajal, A. et al. Glucose-6-phosphate-dehydrogenase on old peroxisomes maintains self-renewal of epithelial stem cells after asymmetric cell division. Nat Commun 16, 3932 (2025). https://doi.org/10.1038/s41467-025-58752-z