Plasticity of the Differentiated State

TLDR

Heterokaryons are used to study how tissue‑specific phenotypes arise and persist. The study aims to isolate genes encoding tissue‑specific trans‑acting regulators that activate muscle genes. Gene expression was examined at single‑cell and bulk levels using monoclonal antibodies and biochemical/molecular assays. Muscle gene expression can be induced in diverse nonmuscle cells, with variable kinetics and dosage requirements, demonstrating that differentiated nuclei are highly plastic and responsive to cytoplasmic cues.

Abstract

Heterokaryons provide a model system in which to examine how tissue-specific phenotypes arise and are maintained. When muscle cells are fused with nonmuscle cells, muscle gene expression is activated in the nonmuscle cell type. Gene expression was studied either at a single cell level with monoclonal antibodies or in mass cultures at a biochemical and molecular level. In all of the nonmuscle cell types tested, including representatives of different embryonic lineages, phenotypes, and developmental stages, muscle gene expression was induced. Differences among cell types in the kinetics, frequency, and gene dosage requirements for gene expression provide clues to the underlying regulatory mechanisms. These results show that the expression of genes in the nuclei of differentiated cells is remarkably plastic and susceptible to modulation by the cytoplasm. The isolation of the genes encoding the tissue-specific trans-acting regulators responsible for muscle gene activation should now be possible.