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

Amanda Whitmill, Ying Liu, Khalid A. Timani, Yinghua Niu, Johnny Jianglin He

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1674-1686
Number of pages13
JournalStem Cells
Volume35
Issue number7
DOIs
StatePublished - 1 Jul 2017

Fingerprint

Stem Cell Factor
Embryonic Stem Cells
Blastocyst
Down-Regulation
Embryonic Development
Embryonic Structures
Genes
tat Gene Products
Biological Phenomena
Zygote
Microarray Analysis
Transgenic Mice
HIV-1
Stem Cells
Growth

Keywords

  • Embryonic development
  • Embryonic stem cells
  • Nanog
  • Oct4
  • Pluripotency
  • Self-renewal
  • Sox2
  • Survival
  • Tip110

Cite this

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title = "Tip110 Deletion Impaired Embryonic and Stem Cell Development Involving Downregulation of Stem Cell Factors Nanog, Oct4, and Sox2",
abstract = "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.",
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Tip110 Deletion Impaired Embryonic and Stem Cell Development Involving Downregulation of Stem Cell Factors Nanog, Oct4, and Sox2. / Whitmill, Amanda; Liu, Ying; Timani, Khalid A.; Niu, Yinghua; He, Johnny Jianglin.

In: Stem Cells, Vol. 35, No. 7, 01.07.2017, p. 1674-1686.

Research output: Contribution to journalArticleResearchpeer-review

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