Transdifferentiation, also known as lineage reprogramming, is the process in which one mature somatic cell is transformed into another mature somatic cell without undergoing an intermediate pluripotent state or progenitor cell type.(a process where one type of fully developed body cell changes directly into another type of body cell, without the cell turning into a stem cell first) It is a type of metaplasia, which includes all cell fate switches, including the interconversion of stem cells.(it's considered as a form of metaplasia, which refers to any change from one kind of cell to another, including changes involving stem cells.) Current uses of transdifferentiation include disease modeling and drug discovery and in the future may include gene therapy and regenerative medicine.(transdifferentiation is currently used in areas like understanding diseases, testing new drugs, and possibly future treatments such as gene therapy and tissue repair). The term 'transdifferentiation' was originally coined by Selman and Kafatos in 1974 to describe a change in cell properties as cuticle-producing cells became salt-secreting cells in silk moths undergoing metamorphosis.

Davis et al. 1987 reported the first instance (sight) of transdifferentiation where a cell changed from one adult cell type to another. Forcing mouse embryonic fibroblasts to express MyoD was found to be sufficient to turn those cells into myoblasts.

The only known instances where adult cells change directly from one lineage to another occurs in the species Turritopsis dohrnii (also known as the immortal jellyfish) and Turritopsis nutricula.

In newts, when the eye lens is removed, pigmented epithelial cells de-differentiate and then redifferentiate into the lens cells. Vincenzo Colucci described this phenomenon in 1891 and Gustav Wolff described the same thing in 1894; the priority issue is examined in Holland (2021).

In humans and mice, it has been demonstrated that alpha cells in the pancreas can spontaneously switch fate and transdifferentiate into beta cells. This has been demonstrated for both healthy and diabetic human and mouse pancreatic islets. While it was previously believed that oesophageal cells were developed from the transdifferentiation of smooth muscle cells, that has been shown to be false.

The first example of functional transdifferentiation has been provided by Ferber et al. by inducing a shift in the developmental fate of cells in the liver and converting them into 'pancreatic beta-cell-like' cells. The cells induced a wide, functional and long-lasting transdifferentiation process that reduced the effects of hyperglycemia in diabetic mice. Moreover, the trans-differentiated beta-like cells were found to be resistant to the autoimmune attack that characterizes type 1 diabetes.

The second step was to undergo transdifferentiation in human specimens. By transducing liver cells with a single gene, Sapir et al. were able to induce human liver cells to transdifferentiate into human beta cells.

This approach has been demonstrated in mice, rat, xenopus and human tissues.