Article

Stem Cell Reviews and Reports

, Volume 10, Issue 2, pp 162-176

Comparative Gene Expression Signature of Pig, Human and Mouse Induced Pluripotent Stem Cell Lines Reveals Insight into Pig Pluripotency Gene Networks

  • Yajun LiuAffiliated withCollege of Veterinary Medicine, Shaanxi Center for Stem Cell Engineering and Technology, Northwest A&F University
  • , Yangyang MaAffiliated withCollege of Veterinary Medicine, Shaanxi Center for Stem Cell Engineering and Technology, Northwest A&F University
  • , Jeong-Yeh YangAffiliated withRegenerative Bioscience Center, University of GeorgiaDepartment of Animal and Dairy Science, University of Georgia, Rhodes Center for Animal and Dairy Science
  • , De ChengAffiliated withCollege of Veterinary Medicine, Shaanxi Center for Stem Cell Engineering and Technology, Northwest A&F UniversityDepartment of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University
  • , Xiaopeng LiuAffiliated withCollege of Veterinary Medicine, Shaanxi Center for Stem Cell Engineering and Technology, Northwest A&F University
  • , Xiaoling MaAffiliated withCollege of Veterinary Medicine, Shaanxi Center for Stem Cell Engineering and Technology, Northwest A&F University
  • , Franklin D. WestAffiliated withRegenerative Bioscience Center, University of GeorgiaDepartment of Animal and Dairy Science, University of Georgia, Rhodes Center for Animal and Dairy Science
  • , Huayan WangAffiliated withCollege of Veterinary Medicine, Shaanxi Center for Stem Cell Engineering and Technology, Northwest A&F UniversityDepartment of Animal Biotechnology, College of Veterinary Medicine, Northwest A&F University Email author 

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Abstract

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.

Keywords

Pig iPS cell GeneChip EpCAM Gene expression profiling