Periodic Reporting for period 4 - Age Asymmetry (Age-Selective Segregation of Organelles)
Berichtszeitraum: 2020-11-01 bis 2021-04-30
In order to undertake their tissue renewing task, stem cells must undergo cell divisions and produce daughter cells that differentiate to the functional cells of the given tissue, and daughter cells that remain as self-renewing stem cells ensuring future tissue renewal. Some stem cells divide asymmetrically to produce these two daughter cells in on division. However, what cellular material is asymmetrically apportioned in such divisions has not been systematically studied, and focus has been on quantitatively asymmetric inheritance of transcription factors. However, we discovered that mitochondria - the organelles central to the cellular metabolism - are segregated qualitatively and age-selectively between daughter cells in asymmetric cell divisions. In this project we study 1) how stem cells recognize the age of their organelles and segregate them age-selectively, 2) what other compartments besides mitochondria are age-selectively segregated, and 3) is age-selective inheritance of organelles lost during aging and can it be promoted to counter aging induced loss of stem cells.
Second, by studying other cellular components, we have discovered that age-selective inheritance is not restricted to mitochondria. Interestingly, while stem cells inherit young mitochondria, they selectively enrich old subpopulation of some other organelles. We are currently analyzing how this opposing age-selective enrichment of various sub-cellular components impacts stem cell function.
Finally, we have generated mouse models that will allow us to address which tissue stem cells segregate organelles age-selective, and whether this novel phenomenon is altered during normal aging and various regenerative programs.