Forcing cells to change lineages

Enforced cell lineage change Though it is important for the success of multicellular organisms that their many different cell types remain stable once specified, advances in the production of induced pluripotent stem (iPS) cells from somatic cells by exposure to a transcription factor cocktail emphasize the potential of almost any cell to be reprogrammed. This raises the question of whether interconversion between cell types occurs physiologically or in the context of disease. Thomas Graf and Tariq Enver use examples from the blood cell system to illustrate the principles of transcription factor transdifferentiation, which they conclude is a process fundamentally similar to differentiation and different from iPS reprogramming. They postulate that conversions of one cell type to another can occur as a normal developmental process, and speculate on the prospects of forced lineage reprogramming in regenerative medicine. The ability to produce stem cells by induced pluripotency (iPS reprogramming) has rekindled an interest in earlier studies showing that transcription factors can directly convert specialized cells from one lineage to another. Lineage reprogramming has become a powerful tool to study cell fate choice during differentiation, akin to inducing mutations for the discovery of gene functions. The lessons learnt provide a rubric for how cells may be manipulated for therapeutic purposes.