High Content Analysis of Human Embryonic Stem Cell Growth and Differentiation

Human embryonic stem cells (hESCs) hold unique promise for regenerative medicine, the treatment of many hematologic malignancies, obtaining information on drug efficacy and toxicity, and understanding fundamental questions in developmental biology. There are two defining characteristics of hESCs, self-renewal without senescence and the ability to change into all lineages of the embryo (pluripotency) and placenta (totipotency). hESCs are an important source of specialized and often limited cell and tissue types in which novel medical therapies can be tested. The use of stem cells in transplantation and tissue engineering is perhaps their most exciting potential therapeutic contribution to the future treatment of injury and disease (1–3). However, more immediate contributions of hESCs will include derivation of reproducible lineages of hepatic (4–6), cardiac (7–10), pancreatic (11), endothelial cells and hematopoietic progenitor cells (12), and neural lineages (13–16) for drug screening and toxicology. Basic science research on ESCs will also advance our knowledge of fundamental principles in cell biology and cell cycle regulation (17, 18). Additionally, epigenetic control of gene silencing (19–22), aging, and senescence (23, 24) will be advanced by their study (18, 25). hESCs are not easily studied, because multiple variables in growth conditions can affect their rates of growth, death, and differentiation. Thus, understanding hESC behavior will require manipulation and analysis of a large number of experimental parameters in order to optimize growth or differentiation conditions. Typically, such experiments involve manually performed, subjective, low throughput analysis