Dedifferentiation

Dedifferentiation is a biological process in which a differentiated, specialized cell loses its distinctive characteristics and reverts to a more primitive, proliferative state. In this deduced state, the cell often regains the capacity to divide and to contribute to tissue regeneration. Dedifferentiation is distinct from transdifferentiation, where a mature cell directly becomes another mature cell type, and from full pluripotent reprogramming, which induces a stem cell state in vitro.

In plants, dedifferentiation is common and forms the basis for callus formation and tissue regeneration. Mature plant tissues can re-enter the cell cycle and generate a mass of undifferentiated cells that can be redirected toward new organs. In animals, evidence of dedifferentiation appears in regenerative contexts such as limb or fin regeneration, where mature cells lose specialized traits and revert to progenitor-like states to form a regrowth structure called a blastema. In mammals, such processes are more limited and context-dependent but remain an active area of research.

Mechanistically, dedifferentiation involves reactivating stem cell programs and extensive remodeling of gene expression. This often includes changes in chromatin accessibility and DNA methylation, along with signaling inputs from the local environment. Pathways such as Wnt, Notch, FGF, and other growth factor signals can promote a more plastic, proliferative state in cells previously on a differentiated trajectory.

The concept has implications for regenerative medicine, wound healing, and tissue engineering, offering potential routes to replace damaged tissues. However, dedifferentiation can also contribute to cancer progression by expanding cellular plasticity and enabling therapy-resistant, stem-like cancer cells. Therapeutic strategies seek to harness controlled dedifferentiation for regeneration while limiting pathological or malignant plasticity.