During the reporting period for this award our team has made substantial progress on the goals for this grant as reflected in four new publications. In a broad sense these studies have enhanced the field’s understanding of the relationship between the molecular machinery in cancer and in stem cells. For example, key molecules that regulate normal pluripotent stem cell behaviors such as self-renewal and pluripotency also have roles in tumorigenesis and our studies have clarified how these regulatory factors (including chromatin and epigenetic factors Myc and histone H3.3) function both normally and in cancer. These studies will have impact both in the cancer stem cell field and for making safer stem cell-based regenerative medicine therapies.

More specifically in Aim 1 we have made progress in determining how H3.3 and Myc function in development and act to control gene expression through genomics studies. In Aim 2, we have made progress in understanding how Myc and its cofactors bind to the genome to regulate epigenetic states and gene expression in human pluripotent stem cells. In Aim 3 we have defined how key novel pluripotency-related oncogenic factors function including DPPA4 and DPPA2 via cutting edge genomics and proteomics studies.