A method for directly converting connective-tissue cells into neurons opened up a new branch of research into cell-based therapies and called into question long-held beliefs about how development affects a cell’s identity.

Our bodies rely on specialized cell types: brain cells compute information, red blood cells bind oxygen, and so on. Because almost all our cells have identical DNA, different patterns of gene and protein expression are needed to define these cell types. The selection and maintenance of these expression cascades were once thought to be irreversible after development. Over time, it emerged that cell identity could be changed, but it was often assumed that a cell could be converted into another cell type only if the two had a similar developmental origin. Ten years ago, Vierbuchen et al. overthrew this idea, by showing that connective-tissue cells called fibroblasts could be converted into functional neurons — which have a very different developmental origin — if they were engineered to express just three extra transcription factors.

This achievement was built on almost a century of visionary experiments in manipulating cell identity. In 1927, Hans Spemann showed that it was possible to change the fate of cells in a salamander embryo. The embryologist grafted ‘organizer’ cells (which drive early development of the body plan) from a donor embryo into a host embryo, triggering the formation of a second embryo from the host cells. In 1962, the biologist John Gurdon showed that development can also be returned to the start — the nucleus of an adult cell can reacquire a state similar to that of cells in the earliest stages of development, and in this state it can give rise to an entire embryo.

In the 1980s, it became clear that cells can also be directly converted from one specialized cell type to another. The first example was the conversion of fibroblasts into muscle cells by inducing the cells to express the transcription factor MyoD. Some years later, a different transcription factor was used to turn non-neuronal cells of the brain called glia into neurons in vitro. The first demonstration that this type of conversion could also occur in vivo in mice opened up a potential new branch of therapy based on converting reactive glia into new neurons after brain insults or neurodegeneration.

 

 

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Nature