Tip110 Deletion Impaired Embryonic and Stem Cell Development Involving Downregulation of Stem Cell Factors Nanog, Oct4, and Sox2

Stem Cells. 2017 Jul;35(7):1674-1686. doi: 10.1002/stem.2631. Epub 2017 May 7.


HIV-1 Tat-interacting protein of 110 kDa, Tip110, plays important roles in multiple biological processes. In this study, we aimed to characterize the function of Tip110 in embryonic development. Transgenic mice lacking expression of a functional Tip110 gene (Tip110-/- ) died post-implantation, and Tip110-/- embryos exhibited developmental arrest between 8.5 and 9.5 days post coitum. However, in vitro cultures of Tip110-/- embryos showed that Tip110 loss did not impair embryo growth from the zygote to the blastocyst. Extended in vitro cultures of Tip110-/- blastocysts showed that Tip110 loss impaired both blastocyst outgrowth and self-renewal and survival of blastocyst-derived embryonic stem cells. Microarray analysis of Tip110-/- embryonic stem cells revealed that Tip110 loss altered differentiation, pluripotency, and cycling of embryonic stem cells and was associated with downregulation of several major stem cell factors including Nanog, Oct4, and Sox2 through a complex network of signaling pathways. Taken together, these findings document for the first time the lethal effects of complete loss of Tip110 on mammalian embryonic development and suggest that Tip110 is an important regulator of not only embryonic development but also stem cell factors. Stem Cells 2017;35:1674-1686.

Keywords: Embryonic development; Embryonic stem cells; Nanog; Oct4; Pluripotency; Self-renewal; Sox2; Survival; Tip110.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blastocyst / metabolism
  • Blastocyst / pathology
  • Cell Differentiation
  • Cells, Cultured
  • Embryo, Mammalian
  • Female
  • Gene Deletion
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Genes, Lethal
  • Mice
  • Mice, Knockout
  • Mouse Embryonic Stem Cells / metabolism*
  • Mouse Embryonic Stem Cells / pathology
  • Nanog Homeobox Protein / genetics*
  • Nanog Homeobox Protein / metabolism
  • Octamer Transcription Factor-3 / genetics*
  • Octamer Transcription Factor-3 / metabolism
  • Pregnancy
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • SOXB1 Transcription Factors / genetics*
  • SOXB1 Transcription Factors / metabolism
  • Signal Transduction


  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • Octamer Transcription Factor-3
  • Pou5f1 protein, mouse
  • RNA-Binding Proteins
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse