An Integrated Approach for Analyzing Stem Cell Differentiation and Lineage Commitment
Speaker: Ipsita Banerjee, Univ. of Pittsburgh
Date & Time: December 2, 2009 - 10:20am
Location: Fiber Optics Auditorium
Embryonic stem cells (ESCs) hold tremendous promise in tissue engineering and regenerative medicine applications because of their unique combination of two properties, pluripotency and an extremely high proliferative capacity. Theoretically, appropriate control of ESC growth and differentiation can lead to almost unlimited supplies of cells and tissues of the desired phenotype. However, ESC systems are still faced with the hurdle of effective protocols that permit robust, large scale culture and expansion of undifferentiated cells to the desired developmental lineages. The overall objective of our research is to study and analyze the process of stem cell differentiation through an integrated experimental and theoretical approach. We primarily focus our attention towards the differentiation of ESCs to pancreatic lineage with potential use in the therapeutic treatment of diabetes. The process of stem cell differentiation has been shown to be induced by both chemical cues as well as modulation of cellular mechanical microenvironments. I will discuss examples that illustrate how each of these microenvironmental stimuli can be incorporated in the culture systems to differentiate the ESCs towards the desired lineage Furthermore, concurrent theoretical analysis of these ESC systems is being developed, to extract useful information from the experimental system which will pave way for mechanistic understanding of the complex process of differentiation. From the standpoint of mechanical microenvironment, we observe a strong effect of substrate mechanical properties on the endodermal differentiation of the ESC. The substrate stiffness is found to modulate cellular morphology, attachment and differentiation pattern. A theoretical approach is being undertaken to understand the mechanism of such complex interactions. From the standpoint of chemical cues, we are investigating the effect of adding chemical inducers and repressors in inducing pancreatic differentiation, using a bottom-up approach. While bottom-up approach is fundamental in capturing regulatory interactions between gene and protein, what is also of interest is the propagation of such information into the tissue or organ level, which modifies the organ functionality. Parallel to the reductionist approach, we are also developing a more holistic picture of cellular interactions in the process of differentiation, which will finally dictate the organ structure and functionality.
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