X-chromosome inactivation in monkey embryos and pluripotent stem cells

Masahito Tachibana, Hong Ma, Michelle L. Sparman, Hyo Sang Lee, Cathy M. Ramsey, Joy S. Woodward, Hathaitip Sritanaudomchai, Keith R. Masterson, Erin E. Wolff, Yibing Jia, Shoukhrat M. Mitalipov

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Inactivation of one X chromosome in female mammals (XX) compensates for the reduced dosage of X-linked gene expression in males (XY). However, the inner cell mass (ICM) of mouse preimplantation blastocysts and their in vitro counterparts, pluripotent embryonic stem cells (ESCs), initially maintain two active X chromosomes (XaXa). Random X chromosome inactivation (XCI) takes place in the ICM lineage after implantation or upon differentiation of ESCs, resulting in mosaic tissues composed of two cell types carrying either maternal or paternal active X chromosomes. While the status of XCI in human embryos and ICMs remains unknown, majority of human female ESCs show non-random XCI. We demonstrate here that rhesus monkey ESCs also display monoallelic expression and methylation of X-linked genes in agreement with non-random XCI. However, XIST and other X-linked genes were expressed from both chromosomes in isolated female monkey ICMs indicating that ex vivo pluripotent cells retain XaXa. Intriguingly, the trophectoderm (TE) in preimplantation monkey blastocysts also expressed X-linked genes from both alleles suggesting that, unlike the mouse, primate TE lineage does not support imprinted paternal XCI. Our results provide insights into the species-specific nature of XCI in the primate system and reveal fundamental epigenetic differences between in vitro and ex vivo primate pluripotent cells.

Original languageEnglish (US)
Pages (from-to)146-155
Number of pages10
JournalDevelopmental Biology
Volume371
Issue number2
DOIs
StatePublished - Nov 15 2012

Keywords

  • Blastocyst
  • Embryonic stem cells
  • Inner cell mass
  • Primates
  • X-inactivation

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Tachibana, M., Ma, H., Sparman, M. L., Lee, H. S., Ramsey, C. M., Woodward, J. S., Sritanaudomchai, H., Masterson, K. R., Wolff, E. E., Jia, Y., & Mitalipov, S. M. (2012). X-chromosome inactivation in monkey embryos and pluripotent stem cells. Developmental Biology, 371(2), 146-155. https://doi.org/10.1016/j.ydbio.2012.08.009