Tissue resident stem cells (aka. adult stem cells) renew and repair our tissues. However, in order to secure tissue homeostasis, generation of new stem cells via self-renewal and their differentiation in to functional cells must be carefully balanced. During aging, multiple types of alterations directly in stem cells, or in their tissue neighbourhood can disturb this balance. Our laboratory studies both stem cell intrinsic, and extrinsic mechanisms altering tissue renewal capacity, and how such mechanisms ultimately result in the functional decline we recognize as aging.
ASYMMETRIC CELL DIVISION
At least some stem cells can divide asymmetrically to generate a new stem cell and a differentiating cell in a predetermined fashion. This raises the question on the nature of factors that are asymmetrically segregated between the two daughter cells predestined with different fates. As aging is primarily caused by accumulation of cellular damage, asymmetric divisions open the opportunity to reduce age-associated damage in the stem cell lineage by segregating damaged components to the differentiating daughter cell.
To probe on this possibility, we develop methods to analyse whether stem cells apportion their organelles qualitatively and selectively upon asymmetric divisions. We have for example discovered that asymmetrically dividing cells with stem cell traits segregate their mitochondria age-selectively and asymmetrically between daughter cells (Katajisto, Science, 2015). More specifically, old mitochondria are segregated away from the stem cell lineage into the differentiating daughter cells. We study how chronologically old organelles differ from newly synthesized ones, and how stem cells sense the age of their organelles. Moreover, we study the mechanisms facilitating age-selective segregation of organelles, and how it impacts function of tissue stem cells, tissue repair, and longevity.
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