Year 2

All of the diverse cells in the human body contain the same genetic information, and originally arose from a single
cell, a fertilized egg. Embryogenesis is a result of cell division followed by differential gene expression, to
selectively activate only the genes needed for development of each specialized cell type. By understanding the
multiple gene activities required to either maintain stem cell pluripotency or effect cell specific differentiation, it
should be possible to define conditions under which undifferentiated stem cells may be grown in large volume in
culture, or induced to become mature cell types of therapeutic interest.

The experiments described in this proposal are directed at understanding the regulation of gene expression in
stem cells as they self-renew, and in the conversion of adult cells back to a stem cell-like state. During this
reporting period we discovered mutations in SCC-A have been linked to dyskeratosis congenital (DC), a genetic
disorder characterized by proliferative defect in stem cells. We were also able to purify SCC-B to homogeneity
which means this could greatly enhance iPSC generation efficiency. SCCs are potential targets for drugs aimed at
increasing or decreasing the ability of stem cells to divide. SCCs could also facilitate the production of high quality
induced pluripotent stem cells for regenerative medicine and tissue replacement therapy.