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Studies

Stem Cell Biology Group

The Stem Cell Biology Group conducts the following studies within the Laboratory of Molecular Carcinogenesis.

 

Genome-wide siRNA screen identified novel self-renewal genes in ES cells

The Stem Cell Biology Group has identified a list of novel candidate genes that are important for mouse embryonic stem (ES) cell self-renewal in a large-scale siRNA screen. Many of these identified genes function in gene regulation and/or development, and are highly expressed in ES cells and embryonic tissues. The group further identified the transcriptional targets of two transcription factors found in the screen, Cnot3 and Trim28, by ChIP-on-chip. Cnot3 and Trim28 co-occupy many gene promoters with two other pluripotency genes c-Myc and Zfx. These four genes form a novel module in the self-renewal transcription network. The group will continue to characterize the genes identified in the screen and study their functions in self-renewal, pluripotency, reprogramming and mouse embryonic development.

 

Development of functional genomic approaches to study stem cell biology

The Stem Cell Biology Group developed a highly parallel multiplex screening method for large-scale genetic screens in mammalian cells. This method makes it possible to carry out rapid and cost-effective genome-wide screens with flexibility in assay design. As a complement to the siRNA screen, the group carried out an shRNA screen using this method to identify genes that affect proliferation, survival and self-renewal in mouse ES cells. The group also collaborated with the lab of Douglas Melton, Ph.D. at Harvard University and carried out a similar screen in human ES cells. From the screens, the group identified a list of candidate genes that have important functions in ES cells. The group will continue to study the functions of these genes in self-renewal, pluripotency, reprogramming and mouse embryonic development. In the long run, the group will also use this screening platform to identify genes that are required for lineage-specification in ES cells and genes that are required for self-renewal and differentiation in adult stem cells.

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