Stem cells are progenitors that maintain stemness (self-renewal) while generating diverse differentiated cell types. Thus, a stem cell's decision to self-renew or to differentiate has profound consequences in development, homeostasis and regeneration. Recently, the role of cancer stem cells in several types of malignancies has been demonstrated; many parallels exist between normal and cancer stem cells - specifically, their ability to self-renew extensively and to generate a wide variety of differentiated cell types. Thus, elucidation of the molecular mechanisms leading to self-renewal or to differentiation is beneficial for both stem and cancer biology. We use Drosophila neural stem cells as a model to study regulation of self-renewal vs. differentiation.
- Neural stem cells
Cheng-Yu Lee uses neural stem cells from the fruit fly Drosophila to study the process of cell self-renewal versus differentiation. By using a combined genetic, biochemical, and genomic approach, Lee wants to understand the specific mechanism of neural stem cells, with implications for human degenerative diseases like Parkinson's.
Drosophila larval brains stained with antibody markers for neural stem cells (green) and neurons (magenta). Wild type brains (left) possess both neural stem cells and a large number of neurons whereas the mutant (right) brains possess mostly neural stem cells and extremely few neurons indicative of failure in differentiation resulting in a stem cell tumor-like phenotype.
Kuang, C., Golden, K.L., Simon, C.R., Damrath, J., Buttitta, L., Gamble, C., & Lee, C.Y. (2014). A novel Fizzy/Cdc20-dependent mechanism suppresses necrosis in neural stem cells. Development 141:1453-64
Komori, H., Xiao, Q., McCartney, B., & Lee, C.Y. (2014). Brain tumor specified intermediate progenitor cells by attenuating β-catenin/Armadillo activity. Development 141:1-12
Xiao, Q., Komori, H. & Lee, C.Y. (2012) klumpfuss distinguishes stem cells from progenitor cells during asymmetric neuroblast division. Development, 139: 2670-2680.
Haenfler, J.M., Kuang, C., & Lee, C.Y. (2012). Cortical aPKC kinase activity distinguishes neural stem cells from progenitor cells by ensuring asymmetric segregation of Numb. Developmental Biology, 365: 219-28.
Weng, M., Haenfler, J.M., & Lee, C.Y. (2011). Changes in Notch signaling coordinates maintenance and differentiation of the Drosophila larval optic lobe neuroepithelia. Dev Neurobiol. 365:219-28