Cell Type of Origin Dictates the Route to Pluripotency

Publication date: 5 December 2017
Source:Cell Reports, Volume 21, Issue 10
Author(s): Christian M. Nefzger, Fernando J. Rossello, Joseph Chen, Xiaodong Liu, Anja S. Knaupp, Jaber Firas, Jacob M. Paynter, Jahnvi Pflueger, Sam Buckberry, Sue Mei Lim, Brenda Williams, Sara Alaei, Keshav Faye-Chauhan, Enrico Petretto, Susan K. Nilsson, Ryan Lister, Mirana Ramialison, David R. Powell, Owen J.L. Rackham, Jose M. Polo
Our current understanding of induced pluripotent stem cell (iPSC) generation has almost entirely been shaped by studies performed on reprogramming fibroblasts. However, whether the resulting model universally applies to the reprogramming process of other cell types is still largely unknown. By characterizing and profiling the reprogramming pathways of fibroblasts, neutrophils, and keratinocytes, we unveil that key events of the process, including loss of original cell identity, mesenchymal to epithelial transition, the extent of developmental reversion, and reactivation of the pluripotency network, are to a large degree cell-type specific. Thus, we reveal limitations for the use of fibroblasts as a universal model for the study of the reprogramming process and provide crucial insights about iPSC generation from alternative cell sources.

Graphical abstract

Teaser

Nefzger et al. find that the molecular reprogramming trajectories of fibroblasts, neutrophils, and keratinocytes have a cell-type-specific component that only fully converges in induced pluripotent stem cells. The authors also identify universal changes shared by all three cell types, including two transcriptional waves and a conserved transcriptional program involving Egr1 downregulation.


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