Highly efficient reprogrammable mouse lines with integrated reporters to track the route to pluripotency

Judith Elbaz, Mira C. Puri, Maryam Faiz, K. W.Annie Bang, Lena Nguyen, Bar Makovoz, Marina Gertsenstein, Samer M.I. Hussein, Peter W. Zandstra, Laurent Briollais, Nika Shakiba, Andras Nagy

Research output: Contribution to journalArticlepeer-review


Revealing the molecular events associated with reprogramming different somatic cell types to pluripotency is critical for understanding the characteristics of induced pluripotent stem cell (iPSC) therapeutic derivatives. Inducible reprogramming factor transgenic cells or animals—designated as secondary (2°) reprogramming systems—not only provide excellent experimental tools for such studies but also offer a strategy to study the variances in cellular reprogramming outcomes due to different in vitro and in vivo environments. To make such studies less cumbersome, it is desirable to have a variety of efficient reprogrammable mouse systems to induce successful mass reprogramming in somatic cell types. Here, we report the development of two transgenic mouse lines from which 2° cells reprogram with unprecedented efficiency. These systems were derived by exposing primary reprogramming cells containing doxycycline-inducible Yamanaka factor expression to a transient interruption in transgene expression, resulting in selection for a subset of clones with robust transgene response. These systems also include reporter genes enabling easy readout of endogenous Oct4 activation (GFP), indicative of pluripotency, and reprogramming transgene expression (mCherry). Notably, somatic cells derived from various fetal and adult tissues from these 2° mouse lines gave rise to highly efficient and rapid reprogramming, with transgene-independent iPSC colonies emerging as early as 1 wk after induction. These mouse lines serve as a powerful tool to explore sources of variability in reprogramming and the mechanistic underpinnings of efficient reprogramming systems.

Original languageEnglish
Article numbere2207824119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number49
StatePublished - 6 Dec 2022
Externally publishedYes


  • induced pluripotent stem cells
  • reprogrammable mouse
  • secondary reprogramming
  • somatic cell reprogramming
  • transgenic mouse


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