Reprogramming roadblocks are system-dependent

Eleni Chantzoura, Stavroula Skylaki, Sergio Menendez, Shin-Il Kim, Anna Johnsson, Sten Linnarsson, Knut Woltjen, Ian Chambers, Keisuke Kaji

Research output: Contribution to journalArticlepeer-review

Abstract

Since the first generation of induced pluripotent stem cells (iPSCs), several reprogramming systems have been used to study its molecular mechanisms. However, the system of choice largely affects the reprogramming efficiency, influencing our view on the mechanisms. Here, we demonstrate that reprogramming triggered by less efficient polycistronic reprogramming cassettes not only highlights mesenchymal-to-epithelial transition (MET) as a roadblock but also faces more severe difficulties to attain a pluripotent state even post-MET. In contrast, more efficient cassettes can reprogram both wild-type and Nanog-/- fibroblasts with comparable efficiencies, routes, and kinetics, unlike the less efficient reprogramming systems. Moreover, we attribute a previously reported variation in the N terminus of KLF4 as a dominant factor underlying these critical differences. Our data establish that some reprogramming roadblocks are system dependent, highlighting the need to pursue mechanistic studies with close attention to the systems to better understand reprogramming.
Original languageEnglish
Pages (from-to)350–364
JournalStem Cell Reports
Volume5
Issue number3
DOIs
Publication statusPublished - 13 Aug 2015

Fingerprint

Dive into the research topics of 'Reprogramming roadblocks are system-dependent'. Together they form a unique fingerprint.

Cite this