International Journal of Molecular Sciences (Oct 2022)

The Defects of Epigenetic Reprogramming in Dox-Dependent Porcine-iPSCs

  • Aiwen Jiang,
  • Yangyang Ma,
  • Xue Zhang,
  • Qianqian Pan,
  • Pengfei Luo,
  • Hongyun Guo,
  • Wangjun Wu,
  • Juan Li,
  • Tong Yu,
  • Honglin Liu

DOI
https://doi.org/10.3390/ijms231911941
Journal volume & issue
Vol. 23, no. 19
p. 11941

Abstract

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Porcine-induced pluripotent stem cells (piPSCs) are of great significance to animal breeding and human medicine; however, an important problem is that the maintenance of piPSCs mainly depends on exogenous expression of pluripotent transcription factors (TFs), and germline transmission-competent piPSCs have not yet been successfully established. In this study, we explore the defect of epigenetic reprogramming during piPSCs formation, including chromatin accessibility, DNA methylation, and imprinted gene expression, with high-throughput sequencing (ATAC-seq, WGBS, RNA-seq, and Re-seq) methods. We found the somatic features were successfully silenced by connecting closed chromatin loci with downregulated genes, while DNA methylation has limited effects on somatic silence. However, the incomplete chromatin remodeling and DNA demethylation in pluripotency genes hinder pluripotent activation, resulting in the low expression of endogenous pluripotency genes. In addition, the expression of potential imprinted genes was abnormal, and many allelic-biased expressed genes in porcine embryonic fibroblasts (PEFs) were erased, accompanied by establishment of new allelic-biased expressed genes in piPSCs. This study reveals the aberrant epigenetic reprogramming during dox-dependent piPSCs formation, which lays the foundation for research of porcine-iPSC reprogramming and genome imprinting.

Keywords