Chapter 15 On Neuronal and Glial Differentiation of a Pluripotent Stem Cell Line, RT4-AC: A Branch Determination

Abstract

Publisher Summary The development of eukaryotes is the result of a series of hierarchical or nonhierarchical branchings of precursor cells (or pluripotent stem cells). Here, hierarchical branching implies that a predetermined order of segregation of cell types exists; nonhierarchical branching means that the order of segregation of cell types from stem cells is not fixed, but is more or less random (stochastic). Nonhierarchical branching has been observed in the branching of certain pluripotent stem cell systems. In this chapter, the term “maturation” is used to describe the cases in which terminal cells express overt differentiation properties in response to external agents, often without cell division. Under maturation conditions, the majority of a homogeneous population of precursor cells responds to an agent and expresses terminal differentiation properties. Detailed studies of neural as well as other characteristics reveal a clear-cut segregation of neuronal and glial properties and tumorigenicity among different derivative cell types upon cell type conversion. In this system, the stem cell type (RT4-AC) expresses some of both neuronal properties and glial properties. The systematic and consistent segregation of these properties is a remarkable and clear phenomenon that alludes to a fundamental aspect of cell differentiation (branch determination), and therefore is worthy of detailed studies on its mechanism. This chapter also observes differential maturational responses of the derivative cell types (RT4-B, RT4-D, and RT4-E) to dibutyryl-CAMP (dbcAMP). Based on the study of this system, the chapter discusses several points about the determination and maturation of neuronal and glial properties.