Embryonic stem cells (ESCs) lie at the top of the stem cell hierarchy with the unique features, immortality and pluripotency. ESCs maintain their identity through indefinite proliferation and have an ability to produce all cell types in our body. Due to these interesting features, ESCs have provided an unprecedented experimental system for cellular and developmental biology and translational medicine. However, fundamental mechanisms governing immortality and pluripotency of ESCs have not been fully understood. Our lab is interested in discovering novel molecular and cellular mechanisms for ESC proliferation and differentiation. Of particular interest is intrapopulation diversity within a stem cell population. How different are single cells in an ESC population? What is biological significance between intra- and inter-population differences? How do single cell phenomena result in population effects? Key problems in the stem cell field such as the maintenance of stemness, differentiation decisions and lineage diversity hinge on how cells resolve these questions. We will use cutting-edge single cell technologies such as single-molecule RNA fluorescence in situ hybridization (smFISH), live-cell imaging, and single cell sequencing to seek answers for these questions. Furthermore, fundamental principles we discovered will be exploited to develop new techniques for therapeutic applications of ESCs.