ESRRB plays a crucial role in the promotion of porcine cell reprograming

J Cell Physiol. 2018 Feb;233(2):1601-1611. doi: 10.1002/jcp.26063. Epub 2017 Jul 31.

Abstract

The estrogen-related receptor b (ESRRB) is an orphan nuclear receptor and targets many genes involved in self-renewal and pluripotency. In mouse ES cells, overexpression of ESRRB can maintain LIF-independent self-renewal in the absence of Nanog. However, the fundamental features of porcine ESRRB remain elusive. In this study, we revealed the expression profiles of ESRRB in both porcine pluripotent stem cells and early stage embryos and dissected the functional domains of ESRRB protein to prove that ESRRB is a key transcription factor that enhanced porcine pluripotent gene activation. Addition of ESRRB into the cocktail of core pluripotent factors Oct4, Sox2, Klf4, and c-Myc (OSKM + E) could significantly enhance the reprograming efficiency and the formation of alkaline phosphatase positive colonies. Conversely, knockdown of ESRRB in piPSCs significantly reduced the expression level of pluripotent genes, minimized the alkaline phosphatase activity, and initiated the porcine induced pluripotent stem cell differentiation. Therefore, porcine ESRRB is a crucial transcription factor to improve the self-renewal of piPSCs.

Keywords: ESRRB; iPS; pig; reprograming; self-renewal.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Cell Self Renewal
  • Cells, Cultured
  • Cellular Reprogramming Techniques
  • Cellular Reprogramming*
  • Gene Expression Regulation, Developmental
  • Induced Pluripotent Stem Cells / metabolism*
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Phenotype
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA Interference
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • Sus scrofa
  • Transfection

Substances

  • KLF4 protein, human
  • Klf4 protein, mouse
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • MYC protein, human
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Proto-Oncogene Proteins c-myc
  • Receptors, Estrogen
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Alkaline Phosphatase