BSC 360: Cell Physiology
BSC 792: Cell Signaling
BSC492/692 Advanced Cell Biology
Embryonic stem cells (ESCs) are characterized by their potential to differentiate into different cell lineages (known as pluripotency) and unlimited capacity for proliferation (known as self-renewal). These properties make them a promising cell source for regenerative medicine. However, we have limited knowledge about basic physiology of ESCs and whether ESC-differentiated cells are fully functional like their in vivo counterparts. The research in Dr. Yanlin Guo’s laboratory focuses on the study of the molecular and cellular mechanisms that control ESC differentiation, with particular interest in cell types for vascular tissue regeneration. Using mouse ESC model, we have developed methods that allow us to generate endothelial cells from ESCs that have the basic properties of naturally differentiated endothelial cells. However, ESC-differentiated cells are unable to mount immune and inflammatory responses when exposed to inflammatory cytokines and infectious agents, which markedly contrasts with naturally differentiated endothelial cells. This finding led to our recent studies demonstrating that the innate immunity is not fully active in ESCs; in particular, ESCs are deficient in expressing type I interferons in response to viruses and synthetic viral RNA analogs. Furthermore, the innate antiviral immunity cannot be properly induced by the current differentiation methods. Conceivably, the lack of innate immunity in ESC-differentiated cells can significantly affect their fate and functionality when used in regenerative medicine. In addition to the significance of this finding in ESC-based regenerative medicine, the lack of innate immunity in ESCs challenges the traditional view in cell biology that all cells have innate immunity. The ongoing projects focus on: 1) elucidating the molecular mechanisms that control innate immunity development during ESC differentiation and 2) developing differentiation strategies that allow generating ESC-differentiated cells with active innate immunity. Dr. Guo’s lab is currently recruiting new graduate students.
Chakraborty, S, Kang, B, Huang, F and Guo,Y-L. Mouse embryonic stem cells lacking p38a and p38d can differentiate to endothelial cells, smooth muscle cells, and epithelial cells. Differentiation 2009, 78: 143-150.
Guo, Y-L, Chakraborty, S, Rajan, S, Wang,R, Huang, F. Effects of oxidative stress on mouse embryonic stem cell proliferation, apoptosis, senescence, and self-renewal. Stem Cells Dev 2010, 19:1321-1331.
Wang, R. and Guo, YL. Transient inhibition of cell proliferation does not compromise self-renewal of mouse embryonic stem cells. Exp Cell Res 2012, 318: 2094-2104.
Wang, R, Wang, J, Amber, P, Acharya, D, Bai, F, Huang, F, and Guo, YL. Antiviral responses in mouse embryonic stem cells: differential development of cellular mechanisms in type I interferon production and response J Biol Chem 2013, 288: 15926-15936
Wang, R, Wang, J, Amber, P, Acharya, D, Bai, F, Huang, F, and Guo, YL. Antiviral responses in mouse embryonic stem cells: differential development of cellular mechanisms in type I interferon production and response J Biol Chem 2014, 289, 25186-25198.
Wang, R, Teng, C, J, Spangler, J, Wang, J, Huang, F, and Guo, YL. Mouse embryonic stem cells have underdeveloped antiviral mechanisms that can be exploited for the development of mRNA-mediated gene expression strategy. Stem Cells Dev 2014, 23: 594-604.