Improving Stem Cell Aging

Throughout life, stem cells are responsible for replenishing and regenerating tissue, fundamentally maintaining "youthfulness." However, with aging, this ability is decreased, resulting in effects such as cognitive impairment, reduced immune response, deterioration of skeletal muscle, and difficulty in wound healing, for example.  Recently, we have shown that neural stem cells (NSCs) asymmetrically segregate cargoes (e.g. ubiquitinated proteins and vimentin) when they divide, leaving one daughter cell more "clean" than the other. In addition, we have identified a diffusion barrier in the endoplasmic reticulum membrane in dividing NSCs that may limit the movement of these cargoes. Indeed, we have found that diffusion barrier strength weakens with age, correlating with a more symmetric distribution of cargoes, suggesting that this may be a mechanism for the segregation (Moore et al, 2015, Science).

In mammalian NSCs, the daughter cell which inherits these cargoes has a slower proliferation rate than the more "clean" daughter, suggesting that this process may be utilized by the cell as a method of cellular rejuvenation (Moore et al, 2015, Science). We hypothesize that stem cells use the asymmetric segregation of cargoes as a mechanism to remain "young," and that loss of this asymmetry and the weakening of the diffusion barrier with age greatly contributes to the stem cell aging phenotype seen in the body.

Research in the Moore lab focuses on identifying the mechanisms that stem cells use to create the asymmetric segregation of cargoes, to identify what other cargoes are segregated, and to use this knowledge to improve stem cell aging. We use mammalian embryonic stem cells and adult NSCs as model systems in our research, with interest in broadening our somatic stem cell portfolio. We employ cell biology, biochemistry, molecular biology, genetics, and computational approaches to address our questions. Our lab specifically focuses on using advanced live imaging technologies, including FLIP, FRAP, photoactivation, 4D timelapse, and computer learning-based high-throughput imaging to interrogate cargoes in mitotic stem cells. If you can see it, you can believe it.

Vimentin (green) is inherited by the non-stem progeny during cell division. mKusabira Orange outlines the apical progenitor.