Transdifferentiation

Abstract The irreversible switch of one differentiated cell type to another is known as transdifferentiation. To consider that such cell‐type switching events arise through mistakes in normal development and tissue repair is a misnomer. It has long been accepted that many invertebrate organisms have the potential for transdifferentiation as part of their normal development or as a mechanism for replacing and regenerating lost or damaged tissue. Although their capacity for transdifferentiation is limited, this is also true for vertebrates and as such, several examples of naturally occurring, experimentally induced and disease‐related cell‐type interconversions have been described for higher organisms. These cell‐type conversions have important implications for understanding normal cell and tissue differentiation, the molecular and cellular basis of disease and may even facilitate the development of novel strategies for cell replacement and gene therapy in regenerative medicine. Key Concepts For a cell‐type conversion to be classified as transdifferentiation, two criteria have to be fulfilled (1) describe the loss of one cell phenotype and the gain of another and (2) demonstrate a direct ancestor–descendant relationship between the two cell types. Transdifferentiation is associated with a discrete change in the programme of gene expression. Transdifferentiation belongs to a broader group of cell type conversions called metaplasias. Metaplasia is derived from the Greek word ‘metaplassein’ meaning ‘to mould into a new form’ and was first used to define the unexpected appearance of foreign tissues in ectopic sites. Metaplasias also includes the conversion of one tissue‐specific stem cell to another tissue stem cell. Some invertebrates demonstrate a remarkable capacity for transdifferentiation as part of their regenerative response to cell or tissue damage. The potential for transdifferentiation in vertebrates is relatively limited compared to invertebrate organisms. During transdifferentiation, cells pass through an intermediate state that may be progenitor‐like or unspecific, the nature of these intermediates is poorly understood.