ID gene expression varies with lineage during differentiation of pluripotential male germ cell tumor cell lines

Human male germ cell tumors (GCTs) comprise an excellent model system for u nderstanding the molecular events controlling cellular differentiation and lineage decision. Pluripotential embryonal carcinoma cell lines derived fro m GCTs can be induced to undergo terminal differentiation along specific li neages dependent upon the differentiating agent. We report here that one su ch cell line, NTera2/clone D1 (NT2/D1), previously shown to undergo differe ntiation along a neuronal lineage by all-trans-retinoic acid (RA), can be i nduced along a distinct non-neuronal lineage by the mammalian morphogens, b one morphogenetic proteins-2 and -4 (BMP-2 and -4). Very little is known re garding the molecular events that govern such human lineage decisions. In t his study, the role of the ID (inhibitor of differentiation and DNA-binding ) family of genes that act as inhibitors of the function of helix-loop-heli x (HLH) transcriptional activators involved in lineage commitment was inves tigated using two pluripotential GCT cell lines as a model system. In the d ifferentiation programs studied, Idl was noted to decline, an event often a ssociated with the decrease in proliferative rate occurring during differen tiation. However, differences in the expression of ID2 and ID3 family membe rs were detected between the programs. Notably, an increase in 1d3 during R A-induced differentiation of NT2/D1 cells was observed, while Id2 levels in creased during BMP-2 and -4 treatment of NT2/D1 cells and during the induct ion of an endodermal-like differentiation program in the cell line, 27X-1. The pluripotential male GCT cell lines comprise a unique system in which th e roles of specific genes such as the ID family of genes in human cell diff erentiation and lineage decision can be studied.