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

Abstract

Human male germ cell tumors (GCTs) comprise an excellent model system for understanding the molecular events controlling cellular differentiation and lineage decision. Pluripotential embryonal carcinoma cell lines derived from GCTs can be induced to undergo terminal differentiation along specific lineages dependent upon the differentiating agent. We report here that one such cell line, NTera2/clone D1 (NT2/D1), previously shown to undergo differentiation along a neuronal lineage by all-trans-retinoic acid (RA), can be induced along a distinct non-neuronal lineage by the mammalian morphogens, bone morphogenetic proteins-2 and -4 (BMP-2 and -4). Very little is known regarding the molecular events that govern such human lineage decisions. In this 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-helix (HLH) transcriptional activators involved in lineage commitment was investigated using two pluripotential GCT cell lines as a model system. In the differetiation programs studied, Id1 was noted to decline, an event often associated with the decrease in proliferative rate occurring during differentiation. However, differences in the expression of ID2 and ID3 family members were detected between the programs. Notably, an increase in Id3 during RA-induced differentiation of NT2/D1 cells was observed, while Id2 levels increased during BMP-2 and -4 treatment of NT2/D1 cells and during the induction of an endodermal-like differentiation program in the cell line, 27X-1. The pluripotential male GCT cell lines comprise a unique system in which the roles of specific genes such as the ID family of genes in human cell differentiation and lineage decision can be studied.

Human tryptophanyl-tRNA synthetase is an IFN-γ–inducible entry factor for Enterovirus

“…29) replicate faster than do NT2 cells (doubling time = 2.29 ± 0.21 days; ref. 30), higher hWARS expression may be required for RD cells to maintain their basal metabolic activity. The differential requirement of hWARS in various cell types, such as muscle cells and neuronal cells, might prevent the identification of important entry factors similar to hWARS in other EV-A71 studies.…”

Cisplatin Induces Resistance by Triggering Differentiation of Testicular Embryonal Carcinoma Cells

“…The effect was actually greater for cDDP than for RA at day 4, but whereas the effect of RA continued to increase by day 10, that of cDDP had begun to fade. The differences between RA- and cDDP- induced expression of differentiation markers suggests that the differentiation program activated by cDDP may differ from that of RA, possibly along a non-neuronal lineage as has been reported for embryonal carcinoma cells following treatment with other agents such as bone morphogenic proteins [22], [23].…”

EZH2 modulates retinoic acid signaling to ensure myotube formation during development

“…Overexpression of Id genes in vitro delays their fusion to form myotubes [ 65 , 66 ]. Additionally, the Id genes are positively regulated by RA signaling, as shown in male germ‐cell tumor cells and promyelocytic leukemia cells [ 68 , 69 ]. Finally, Ezh2 ablation leads to ectopic upregulation in Id genes during development and cancer [ 50 , 70 ].…”