Jak/Stat3 regulated global gene expression dynamics during late-stage reprogramming process

We performed RNAseq analysis to dissect the dynamic transcriptome change during mouse iPSC induction, with or without blocking the Jak/Stat3 activity. We described Jak/Stat3 activity-specific global gene expression patterns, biological events, and regulation of key pluripotent genes, epigenetic modulators, and non-coding RNAs during the reprogramming process. We further demonstrated that Jak/Stat3 activity is essential for proper imprint of Dlk1-Dio3 region that is necessary for complete pluripotency establishment. Functional analysis revealed that one Jak/Stat3 downstream targets identified in our study - Esrrb significantly rescues reprogramming despite the inhibition of Jak/Stat3 activity. Our data illustrated novel mechanism in Jak/Stat3 promoted pluripotency establishment, which is valuable for further improvement of naïve-state iPSC generation across different species. Examination of the RNA samples collected from reprogrammed cells at 18 days after retroviral OKSM transduction of OG-MEFs and cultured in reprogramming medium with LIF, with either Jaki or DMSO (control) treatment starting at day 3 (named hereafter Jaki-Stage 1 (S1) or DMSO-S1, respectively), or from iPSC colonies picked at day 21 and expanded one more passage (p2) (named hereafter Jaki-S2 or DMSO-S2, respectively)