Title : Uncover the power of stem cells: Understanding ESC self-renewal, pluripontency, and differentiation
Speaker: Guang Hu
Host: Prof. Yuan Wang
When: 2012-12-10 15:00
Where: Conference Room 534, School of Life Sciences
Abstract：Pluripotent stem cells, such as embryonic stem cells (ESCs), can be used to model mammalian embryonic development, and to derive various cell types for disease investigation, drug discovery, regenerative medicine, toxicology and environmental health studies. To fully realize the potential of the pluripotent stem cells, it is important to understand the molecular basis of their defining features: self-renewal, pluripotency, and differentiation.To systematically study self-renewal and pluripotency, we have previously carried out a genome-wide RNAi screen in mouse ESCs and identified a list of novel candidate genes that are important for ESC maintenance. We are now investigating the function of several of these candidates in ESCs and mouse embryonic development, with the hypothesis that ESC self-renewal and pluripotency are regulated at different levels by an orchestra of multiple factors and pathways. To date, we found that three members of the Ccr4-Not complex, Cnot1, Cnot2, and Cnot3, play critical roles in maintaining mouse and human ESC identity as a protein complex and inhibit differentiation into the extraembryonic lineages. They are enriched in the inner cell mass of blastocysts, highly expressed in ESCs, and down-regulated during differentiation. Interestingly, Cnot1, Cnot2, and Cnot3 do not act through the known self-renewal pathways or core transcription factors. Instead, they maintain self-renewal possibly by repressing the expression of extraembryonic transcription factors. Finally, in addition to its function in self-renewal, we found that one of the Cnot genes, Cnot3, also plays important roles in ESC differentiation toward the cardiomyocyte lineage. We propose that Cnot3 is a critical factor during normal heart development. Through these studies, we hope to provide a more complete view of the molecular mechanism of self-renewal, pluripotency, and differentiation, and thereby facilitate the use of pluripotent stem cells in research and therapeutic applications. Furthermore, we hope to establish in vitro culture models for the systematic study of the effect of environmental factors on human development and diseases.