Transdifferentiation: do transition states lie on the path of development?

The direct conversion of one differentiated cell fate into another identity is a process known as Transdifferentiation. During Transdifferentiation, cells pass through intermediate states that are not well understood. Given the potential application of transdifferentiation in regenerative medicine and disease modeling, a better understanding of intermediate states is crucial to avoid uncontrolled conversion or proliferation, which pose a risk for patients. Researchers have begun to analyze the transcriptomes of donor, converting and target cells of Transdifferentiation with single cell resolution to compare transitional states to those found along the path of development. Here, we review examples of Transdifferentiation in a range of model systems and organisms. We propose that cells pass either through a mixed, unspecific intermediate or progenitor-like state during Transdifferentiation, which, to varying degrees, resemble states seen during development.