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Highlighting Cell-Specific Paths of the Reprogramming Journey



Review of “Cell Type of Origin Dictates the Route to Pluripotency” from Cell Reports by Stuart P. Atkinson

While each journey we take is never the same, we pass through similar roads and overcome similar obstacles wherever we go. Now, after a new study in Cell Reports, we now know that for our day-to-day trips and the epic odysseys endured by somatic cells during reprogramming to pluripotency, the starting point appears to be the most significant influence on the journey taken!

In short, researchers from the laboratories of Owen J.L. Rackham (Duke-National University of Singapore Medical School) and Jose M. Polo (Monash University, Australia) assessed the reprogramming process of various mouse somatic cell types (fibroblasts, neutrophils, and keratinocytes) in an attempt to highlight both the “universal” and the “cell-specific” parts of the reprogramming journey [1].

Nefzger et al. discovered that two waves of transcription characterized the acquisition of pluripotency in all three cell types following the synchronized induction of reprogramming factor (OSKM) expression. The first wave allows the cells to “shake off” their previous identity, while the second reactivates the genes required for the pluripotency network to function. However, while OSKM expression induced a partially conserved transcriptional signature during reprogramming, including the universal requirement for Egr1 downregulation [2], each cell displayed cell-type-specific transcriptional changes related to their initial identity (or journey starting point!). Furthermore, the authors established that a transition through a primitive streak-like state, previously identified as a universal feature of mammalian cell reprogramming [3], did not occur in neutrophils and keratinocytes, again suggesting that the starting point profoundly influences the reprogramming journey.

The take-home message from this exciting new study is clear to see: going beyond fibroblasts as a model cell may shed new light on the intricate mechanisms behind the reprogramming process. 

For more on the cell-specific and universal mechanisms at play behind reprogramming to pluripotency, stay tuned to the Stem Cells Portal.


  1. Nefzger CM, Rossello FJ, Chen J, et al., Cell Type of Origin Dictates the Route to Pluripotency. Cell Reports;21:2649-2660.
  2. Worringer Kathleen A, Rand Tim A, Hayashi Y, et al., The let-7/LIN-41 Pathway Regulates Reprogramming to Human Induced Pluripotent Stem Cells by Controlling Expression of Prodifferentiation Genes. Cell Stem Cell;14:40-52.
  3. Takahashi K, Tanabe K, Ohnuki M, et al., Induction of pluripotency in human somatic cells via a transient state resembling primitive streak-like mesendoderm. Nature Communications 2014;5:3678.