Correlated time-lapse imaging and single cell molecular analysis of human embryo development

We understand little about human development especially at the earliest stages. Yet human developmental biology is very important to stem cell biology and regenerative medicine for two reasons: 1) Understanding human developmental pathways especially of embryonic differentiation will inform our efforts to derive pluripotent stem cells and differentiate them to stable progenitors that are suitable for transplantation or pharmaceutical applications. Clearly, human development follows well-defined pathways that we are just beginning to elucidate. 2) Understanding human development will allow us to translate findings to the clinic to alleviate common problems of women's and children's health. Errors in the earliest stages of development are the most common cause of all birth defects in the human population and yet we know little of the fundamental ways in which errors occur. Our lack of knowledge is likely enhanced by the complete ban of federal funding for this research in spite of the fact that each year there is increased clinical use of procedures such as IVF. Thus, here we seek to build a map of human development that combines imaging (microscopic) data, molecular data, genetic and epigenetic data to describe human pluripotent blastomeres (cells) and their potentials. We note that events in the first few cell divisions, even before human embryos turn on their own genes, have repercussions to later generations of cells and the overall health and welfare of the embryo and fetus (and likely adult). Our goals are based on our research over several years in which we initiated construction of a map of pathways and programs that function during embryo development. Our studies provide methods and algorithms for early diagnosis of embryo potential in clinics and should be extended to the diagnosis of the general health of pluripotent stem cell populations. We expect that via translation of our basic studies to the clinic, we will improve outcomes of IVF in terms of birth of healthy offspring and decrease devastating and common adverse outcomes such as multiple births with attending complications to organ development, epigenetic errors that may result in miscarriage, and need to reduce fetal number to increase odds of survival of siblings and/or mother. Thus, this research may yield benefits to both maternal/fetal health and stem cell biology and regenerative medicine.