Nervous System-Specific Proteins in Cultured Neural Cells

Results clearly demonstrated that selective overgrowth was responsible for the observed “dedifferentiation” in some cases; growth in culture did not ipso facto mean loss of function for the progeny of a functional cell.

Abstract

The earliest reports of differentiated functions in serially cultured cell strains and lines are difficult to trace completely and depend to some degree on an acceptable definition of the term "differentiated." Should we, for example, consider the species and strain-specific antigens of cells as "functional" or #x201C;differentiated" markers? Several early references describe serially cultured cells which maintained such antigenic distinctions (Brand and Syverton, 1960; Stulberg, et al., 1961; Coombs, 1962). The consensus arising from an analysis of much of the cell culture studies of the 1950s and early 1960s, however, suggested that serially cultured cells generally lose the ability to carry out differentiated functions characteristic of their tissue of origin. Occasional reports to the contrary, the loss of differentiated function was thought to be a relatively general feature of dispersed cell culture. In the early 1960s loss of function in cultured cells was ascribed to two different mechanisms. The first of these phenomena was termed #x201C;dedifferentiation," a process inherent in cells propagated in dispersed culture. Alternatively, selective overgrowth by undifferentiated cells in the mixed cultures was postulated as the factor responsible for loss of function. The review of Levintow and Eagle (1961) describes the debate over these two phenomena as it existed at that time, while Yasumura (1968) provides a retrospective discussion of the controversy. Sato and his associates were able to resolve at least some aspects of this debate when they isolated from neoplasms of various endocrine organs a variety of clonal cell strains which were capable of producing organ-specific products in culture (Buonassisi et al., 1962; Yasumura et al., 1966). These results clearly demonstrated that selective overgrowth was responsible for the observed "dedifferentiation" in some cases; growth in culture did not ipso facto mean loss of function for the progeny of a functional cell. The clonal isolation of functional cell strains from neoplastic tissue has since become a major tool in a number of areas, including cell biology, endocrinology, and, most recently, neurobiology.