Cell fate determination was once thought to be unidirectional [18] , that is, as progenitor cells differentiate there is a progressive and permanent inactivation of specific genes that allow for their potency. However, technological advances suggest this is not strictly the case. Pioneering experiments of nuclear reprogramming utilized cell fusion to demonstrate that cytoplasmic elements of one fusion partner can impact nuclear transcription factors of the other fusion partner, inducing programming or reprogramming [19] [20] [21] . Later studies pinpointed specific transcription factors that, when activated exogenously, can fully reprogram somatic cells to an embryonic-like state [22] [23] [24] [25] [26] . Though successful reprogramming has been realized with this tailored in vitro approach, programming may require greater temporal control. Spontaneous physiologic cell-cell fusion is a temporally and spatially regulated process essential for programming or 2 Stem Cells International differentiation of certain cell types [27, 28] . Thus cell fusion may also confer a regulated transfer of transcriptional control necessary to drive stem cell or progenitor cell differentiation for repair of tissues in mature animals.