Transdifferentiation

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Transdifferentiation in biology takes place when a non-stem cell transforms into a different type of cell, or when an already differentiated stem cell creates cells outside its already established differentiation. Developmental biologist and biochemist David Tosh has restricted the definition of transdifferentiation to irreversible switches of one differentiated cell type to another. Transdifferentiation is a type of metaplasia, which includes all cell fate switches, including the interconversion of stem cells.

Transdifferentiation takes place in nature in a few specific cases. For example, in salamanders and chickens when the lens of the eye is removed, cells of the iris turn into lens cells. Still, such naturally occurring cases, or even ones created in the laboratory are rare.

Until recently, biologists were not much interested in the matter, believing it to be something without much practical consequence. However, around 2001 biologist Philippe Collas published results that seem to show that some cells can be transformed into other types of cells.

The scientists at the biotechnology firm Nucleotech demonstrated in vitro reprogramming of fibroblasts by first creating tiny pores in the cells through reversible permeabilization and then exposing the permeabilized cells to an extract derived from immune cells containing a mixture of regulatory factors but no genetic material. The reprogrammed cells were removed from the extract, resealed and grown in a culture. As a result, in less than an hour's time the regulatory factors were actively taken up by the nucleus causing the fibroblast cells to express molecules and functions characteristic to immune cells while down-regulating the original cells' typically expressed genes.

Many biologists are still skeptical. They say the transdifferentiation that Collas has shown are not complete - the cells did switch on some of the genes that would be used in their 'new' type but not in their 'old', but they did not switch off all of their old genes. It is still an open question whether transdifferentiation could cause a complete change of cell type, and whether such a change would remain active after the cell has been re-implanted in the body.

Although transdifferentiation is rare in vertebrates, it occurs in the fetal development of the esophagus, when the tunica muscularis which is comprised of smooth muscle transdifferentiates into skeletal muscle across:

The entire wall of the esophagus (ruminants, dog)
The entire wall excluding the stomach junction (pig) or
The cranial 2/3 of the esophageal wall (cat, horse).

During this process, smooth muscle cells transform back into myoblasts, then line up and fuse to form myotubes which then become cylindrical skeletal muscle fibers.

Evidence for transdifferentiation in adult humans is given by Barrett's metaplasia in which epithelieal cells of the esophagus switch to intestinal mucin-secreting goblet cells. Barrett's metaplasia predisposes people to adenocarcinoma, with an 80% mortality rate.