We are interested in understanding in molecular details of two key properties of stem cells. First, self renewal is defined as the ability of stem cells to divide indefinitely, in contrast to non-stem cells which are limited in their ability to divide. Second, pluripotentiality refers to the ability of stem cells to differentiate in all cell types that are present in an adult organism. There is growing evidence that these two properties of stem cells are controlled at the central level via the interplay of cellular factors that control the transfer of DNA into RNA. Several key transcription factors have been identified that are unique to stem cells. Our laboratory has specialized during the last 20 years in the study of a family of proteins called histone deacetylases that control the activity of many transcription factors. However, no data exist on the possible role of these proteins in the self renewal and pluripotentiality of stem cells. We propose a series of experiments that will explore the role of histone deacetylases in these critical properties of stem cells. This information will ultimately advance our efforts at generating stem cells with therapeutic potential for use in the clinic.