However, exceptions to the loss of plasticity associated with such lineage restrictions have long been recognized in disease and repair. For example, the epithelium that lines the lungs of smokers is often seen to change from simple columnar cells to a stratifed configuration (a process called squamous metaplasia), and bone can be formed in injured skeletal muscle (osseous metaplasia). Experimentally, heterokaryons, which are created by transferring a nucleus from a cell of one type into a cell of a different type, show changes in nuclear gene expression that reflect the character of the host cell, demonstrating that differentiation is an actively maintained, dynamic state rather than a one-way street.

With the blossoming of stem-cell research, demonstrations of heretofore implausible genomic plasticity are now published almost weekly. Many reports describe the derivation of cells of several tissues from a single source population. Although the mechanisms of genomic plasticity remain poorly understood, the presence of plasticity suggests that gene-restriction mechanisms are not irreversible after all.

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