Although many approaches have been employed to generate defined fate in vitro, the resultant cells often appear developmentally immature or incompletely specified, limiting their utility. Growing evidence suggests that current methods of direct lineage conversion may rely on the transition through a developmental intermediate. Here, I hypothesize that complete conversion between cell fates is more probable and feasible via reversion to a developmentally immature state. I posit that this is due to the role of pioneer transcription factors in engaging silent, unmarked chromatin and activating hierarchical gene regulatory networks responsible for embryonic patterning. Understanding these developmental contexts will be essential for the precise engineering of cell identity.

Original languageEnglish
Pages (from-to)2696-2705
Number of pages10
JournalDevelopment (Cambridge)
Issue number15
StatePublished - Aug 1 2016


  • Cell fate engineering
  • Direct lineage reprogramming
  • Gene regulatory networks
  • Pioneer transcription factors


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