In our write-up of the last ISSCR meeting, Natalie DeWitt and I described Thomas Graf’s, Doug Melton’s, and others’ work to change cell fate. We asked people to weigh in on preferred terms.

Graf sent us this thoughtful response:

Dear Monya, Dear Natalie,

I would like to comment on the issue that you brought up in the last edition of Nature Report Stem Cells.

‘Are the terms reprogramming or trans-differentiation appropriate in describing the transition from one differentiated cell type into another? Should another term be used instead? ‘

In my opinion, this discussion comes too early. We simply don’t know enough about what happens when a differentiated cells acquires a new fate. If, unlike during induction of iPS cell formation, the cells directly transit from one phenotype into another probably a term other than ‘reprogramming’ would be more appropriate. Indeed, the frequency and timing by which transcription factor induced lineage conversions can be observed makes it unlikely that the cells transiently acquire an ES like state. However, it is still possible that when one lineage turns into another the cells go back to the stage of a common precursor before they re-commit. If this would be the case- should it be called ‘reprogramming’? The other possibility is that we will increasingly see induced cell fate conversions in which the new phenotypes generated only partially recapitulate known stages of differentiation. Would it make sense to coin different terms to distinguish these diverse processes?

For the time being the non committal term ‘conversion’ seems appropriate in all instances that do not involve iPS cell reprogramming.

Thomas Graf

Center for Genomic Regulation, CRG

Carrer Dr. Aiguader 88

E 08003 Barcelona

Spain