Periodic Reporting for period 1 - Geometric fate (Niche geometry as the regulator of communal metabolism and cell fate)
Période du rapport: 2022-06-01 au 2024-11-30
Stem cells and differentiated cells have different metabolic demands and we recently discovered that certain stem cells can direct the fate of their daughter cell progeny by segregating metabolically distinct mitochondria, the organelles central to cellular metabolism, asymmetrically between the two daughter cells (Döhla et al. Nature Cell Biology 2022). Thus, at least in some stem cell divisions, metabolism could be among the first traits that drive distinction between self-renewal and differentiation.
Tissue stem cells are found in specialized compartments or niches that are usually highly spatially organized, with stem cells and specialized cells running their different metabolism side by side. Differentiated cells of the niche are important for maintaining stem cell function, but to what extend this is linked to the metabolic needs of the cell types has not been systematically studied. In this project we study how metabolic traits separated when a stem cell divides turn into differences in daughter cell function and to what extent this is supported by the organization and metabolism of the stem cell niche in a tissue.
Furthermore, we have already found that the shape of the stem cell niche can facilitate communication between stem cells and their differentiated neighbours and that organelles responsible for cell-to-cell signalling, Golgi, are highly organized to optimize stem cell function in a tissue. Importantly, the spatial organization, both of the tissue niche and the Golgi, is disrupted in old animals, with implications for tissue renewal capacity. Currently we are studying to what extent this is linked to the different metabolic properties of the cells in the tissue.