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Darcie Moore

Darcie L. Moore

PhD, University of Miami, Florida
Assistant Professor, Dept. of Neuroscience
Affiliate Faculty, Cell and Regenerative Biology

Stem Cell Aging

Neural stem cells (NSCs) in the adult hippocampus proliferate throughout life and generate new neurons. This process, called "adult neurogenesis," is critically involved in certain forms of hippocampus-dependent learning and memory. Failing neurogenesis has been associated with a number of diseases such as major depression and cognitive aging, though the mechanisms behind this dysfunction are not well understood.

In budding yeast division, the mother yeast cell can asymmetrically retain aging factors, leaving the daughter cell free of damage due in part to the presence of a diffusion barrier (Shcheprova et al., 2008). Recently, we have shown that mammalian NSCs also possess a diffusion barrier during mitosis. Barrier strength is regulated with age, such that NSCs from old animals possess a weak, or leaky diffusion barrier, potentially allowing molecules to pass more freely between the daughter cells (Moore et al., 2015).

We have found that one of the cargoes that are asymmetrically segregated between the progeny is ubiquitinated proteins. These damaged proteins are asymmetrically segregated between the progeny such that the daughter that would go on to become a neuron is more likely to receive the "junk," while the daughter that would remain a stem cell is more "clean." With age, and a weakening of the diffusion barrier, this junk is more likely to be inherited by the stem cell as well, leading to a reduction in proliferation rate (Moore et al., 2015).

These findings suggest not only that young NSCs possess a mechanism to rejuvenate themselves, but also that the dysfunction of this process with age may be a possible explanation for why there is an age-dependent decrease in adult neurogenesis in the brain.

Our present research seeks to understand the molecular mechanisms behind these processes, identify what other cargoes are segregated, and to use this knowledge to rejuvenate NSC function in the aging brain. Finally, we are asking if this process of asymmetric segregation as a method of rejuvenation is present in all stem cells, or even all proliferating cells.

Representative Publications
Moore, D. L., & Jessberger, S. (2017). Creating age asymmetry: Consequences of inheriting damaged goods in mammalian cells. Trends in Cell Biology, 27(1), 82-92.
View publication via DOI: DOI:10.1016/j.tcb.2016.09.007

Beckervordersandforth, R., Ebert, B., Schaffner, I., Moss, J., Fiebig, C., Shin, J., Moore, D.L., Ghosh, L., Trinchero, M.F., Stockburger, C., Friedland, K., Steib, K., von Wittgenstein, J., Keiner, S., Redecker, C., Holter, S.M., Xiang, W., Wurst, W., Ja (2017). Role of mitochondrial metabolism in the control of early lineage progression and aging phenotypes in adult hippocampal neurogenesis. Neuron, 93(3): 560-573.
View publication via DOI: DOI:10.1016/j.neuron.2016.12.017

Moore, D.L., Pilz, G.A., Arauzo-Bravo, M.J., Barral, Y., & Jessberger, S. (2015). A mechanism for the segregation of age in mammalian neural stem cells. Science, 349(6254), 1334-1338.
View publication via DOI: DOI:10.1126/science.aac9868

Moore, D.L., & Jessberger, S. (2013). All astrocytes are not created equal - the role of astroglia in brain injury. EMBO Reports, 14(6), 487-8.
View publication via DOI: DOI:10.1038/embor.2013.54

Moore, D.L., & Goldberg, J.L. (2011). Multiple transcription factor families regulate axon growth and regeneration. Developmental Neurobiology, 71(12): 1186-211.
View publication via DOI: DOI:10.1002/dneu.20934

Moore, D.L., Apara, A., & Goldberg, J.L. (2011). Kruppel-Like Transcription Factors in the Nervous System: Novel players in neurite outgrowth and axon regeneration. Molecular and Cellular Neuroscience, 47(4), 233-43.
View publication via DOI: DOI:10.1016/j.mcn.2011.05.005

Blackmore, M.G., Moore, D.L., Smith, R.P., Goldberg, J.L., Bixby, J.L., & Lemmon, V.P. (2010). High content screening of cortical neurons identifies novel regulators of axon growth. Molecular and Cellular Neuroscience, 44(1), 43-54.
View publication via DOI: DOI:10.1016/j.mcn.2010.02.002

Moore, D. L., & Goldberg, J.L. (2010). Four steps to optic nerve regeneration. Journal of Neuro-ophthalmology, 30(4), 347-60.
View publication via DOI: DOI:10.1097/WNO.0b013e3181e755af

Moore, D.L., Blackmore, M.G., Hu, Y., Kaestner, K.H., Bixby, J.L., Lemmon, V.P., & Goldberg, J.L. (2009). KLF Family Members Regulate Intrinsic Axon Regeneration Ability. Science, 326(5950), 298-301.
View publication via DOI: DOI:10.1126/science.1175737

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