Reported pig induced pluripotent stem cells (piPSCs) have shown either a 
bFGF-dependent state with human embryonic stem cell (ESC) and mouse epiblast 
stem cell (EpiSC) morphology and molecular features or piPSCs exist in a 
LIF-dependent state and resemble fully reprogrammed mouse iPSCs. The features of 
authentic piPSCs and molecular events during the reprogramming are largely 
unknown. In this study, we assessed the transcriptome profile of multiple piPSC 
lines derived from different laboratories worldwide and compared to mouse and 
human iPSCs to determine the molecular signaling pathways that might play a 
central role in authentic piPSCs. The results demonstrated that the 
up-regulation of endogenous epithelial cells adhesion molecule (EpCAM) was 
correlated with the pluripotent state of pig pluripotent cells, which could be 
utilized as a marker for evaluating pig cell reprogramming. Comparison of key 
signaling pathways JAK-STAT, NOTCH, TGFB1, WNT and VEGF in pig, mouse and human 
iPSCs showed that the core transcriptional network to maintain pluripotency and 
self-renewal in pig were different from that in mouse, but had significant 
similarities to human. Pig iPSCs, which lacked expression of specific naïve 
state markers KLF2/4/5 and TBX3, but expressed the primed state markers of Otx2 
and Fabp7, share defining features with human ESCs and mouse EpiSCs. The cluster 
of imprinted genes delineated by the delta-like homolog 1 gene and the type III 
iodothyronine deiodinase gene (DLK1-DIO3) were silenced in piPSCs as previously 
seen in mouse iPSCs that have limited ability to contribute to chimaeras. These 
key differences in naïve state gene and imprinting gene expression suggests that 
so far known piPSC lines may be more similar to primed state cells. The primed 
state of these cells may potentially explain the rare ability of piPSCS to 
generate chimeras and cloned offspring.