Cloned human teratoma cells differentiate into neuron-like cells and other cell types in retinoic acid

Abstract

ABSTRACT Single cell clones were isolated from the human teratoma line, Tera-2. The cells of three of these clones were studied. The progressively growing cells were shown to be tumorigenic, and they were characterized by the lack of expression of β 2β2-microglobulinand HLA-A,B,C determinants on the cell surface. The majority of the cells expressed Thy-1 antigen and a 90 × 103 molecular weight protein recognized by the monoclonal antibody F10.44.2; between a third and half of the cells expressed the sugar specificities detected by the anti-SSEA-1 monoclonal antibody. In response to 5 × 10−5 M-retinoic acid applied to cells in monolayer culture, the cells differentiated into a population of flat static cells arrested in the GI phase of the cell cycle. A substantial proportion of these differentiated cells expressed β 2-microglobulin and 43 × 103 molecular weight HLA-A,B,C polypeptides, Thy-1, SSEA-1 sugar determinants, and the 90 × 103 protein recognized by F10.44.2. The apparent molecular weight of fibronectin secreted by the cells decreased by about 5 × 103Mr to 235 × 103Mr after differentiation. The progressively growing cells lacked reactivity with reagents that mark cells in the nervous system. Following aggregation and retinoic acid treatment, neuron-like cells were formed. These cells reacted with reagents that also react with human neurons in culture: they reacted with tetanus toxin, the anti-neurofilament antibodies BF10 and RT97, the anti-ganglioside, GQlc antibody F12 A2B5, and anti-Thy-1. The progressively growing cells of these Tera-2 clones are therefore capable of forming at least two types of cell: the flat cells in monolayer cultures and the neuron-like cells. None of the cell populations reacted with the monoclonal antibody against SSEA-3 and these cloned cells are therefore distinct from previous isolates from Tera-2.