dedifferentiated

Dedifferentiated is an adjective used to describe cells or tissues that have lost their mature, specialized characteristics and returned to a more primitive, progenitor-like state. Dedifferentiation is the reverse of differentiation, representing a shift toward less specialized gene expression and cellular behavior.

In development and regeneration, dedifferentiation is observed in various organisms. For example, some amphibians regenerate limbs through dedifferentiation of mature cells at the injury site into a proliferative blastema, which then differentiates to restore tissues. In plants, mature cells can re-enter the cell cycle and form callus tissue; this process underlies many plant tissue culture techniques and organ formation.

Mechanisms of dedifferentiation include epigenetic remodeling, transcriptional reprogramming, and activation of stem-cell–associated pathways. Signals such as Wnt, Notch, and growth factors can promote dedifferentiation, while chromatin remodeling and changes in DNA methylation enable a more plastic transcriptional program and cell-cycle re-entry.

In pathology, dedifferentiation is common in cancer, where tumor cells may lose lineage-specific traits and acquire stem-like features. Dedifferentiated cancer cells often exhibit increased plasticity, invasiveness, and resistance to therapies; understanding this process is a focus of regenerative medicine and oncology.

A related concept is transdifferentiation, in which a mature cell directly switches to another lineage without passing through a progenitor state. Dedifferentiation can be reversible or context-dependent and is influenced by the tissue environment and injury.