As noted in our application, human embryo development is poorly understood in spite of its central importance to our understanding of the natural programs and mechanisms of human nuclear reprogramming and cell fate decisions, subjects critical to stem cell biology and regenerative medicine. Thus we sought to address the hypothesis that knowledge of human embryo development can be translated to improved clinical applications in both reproductive and regenerative medicine. Further, we hypothesized that the native programs of the human oocyte to embryo transition can inform our understanding and practices in human pluripotent stem cell biology. We proposed three aims to address our hypothesis, as follows: Specific Aim 1) Examine developmental genetic programs to identify factors required to activate the human embryonic genome. Here, we proposed to uncover the relationships between imaging parameters, mRNA programs especially degradation and EGA, and epigenetic programs. We test the hypothesis that destruction of maternal RNAs occurs concurrently with epigenetic remodeling and is a prerequisite for EGA through modeling. Specific Aim 2) Determine the relationship between predictive imaging parameters and aneuploidy. Here we proposed to examine the relationship between embryonic cell behaviors and underlying chromosomal composition and then develop a fully-automated algorithm that allows non-invasive diagnosis of viability and aneuploidy in single cells. Specific Aim 3) Extend our findings to human pluripotent stem cells. We have made substantial progress on all three aims, in particular in examining epigenetic programs of human embryos, examining the relationship between aneuploidy and imaging behavior and deriving methods amenable to screening of new factors that may impact pluripotent line characteristics.