X-chromosome inactivation in monkey embryos and pluripotent stem cells

Area of Science:

• Epigenetics
• Developmental Biology
• Genetics

Background:

• Mammalian females (XX) inactivate one X chromosome to balance gene dosage with males (XY).
• Pluripotent cells like mouse embryonic stem cells (ESCs) and inner cell mass (ICM) initially have two active X chromosomes (XaXa).
• X chromosome inactivation (XCI) in mice occurs randomly after implantation or ESC differentiation, creating mosaic tissues.

Purpose of the Study:

• To investigate X chromosome inactivation (XCI) patterns in rhesus monkey ESCs and early embryonic tissues.
• To compare XCI in primate pluripotent cells with established patterns in mice.
• To understand species-specific differences in XCI during primate development and in vitro culture.

Main Methods:

• Analysis of X-linked gene expression and methylation in rhesus monkey ESCs.
• Examination of XIST and other X-linked gene expression in isolated female monkey ICMs.
• Investigation of X-linked gene expression in preimplantation monkey trophectoderm (TE).

Main Results:

• Rhesus monkey ESCs exhibit monoallelic expression and methylation, consistent with non-random XCI.
• Isolated female monkey ICMs express X-linked genes from both X chromosomes, indicating retained XaXa status.
• Primate trophectoderm (TE) expresses X-linked genes from both alleles, suggesting no imprinted paternal XCI, contrasting with mice.

Conclusions:

• Rhesus monkey ESCs display non-random XCI, similar to human ESCs.
• Ex vivo primate pluripotent cells (ICMs) maintain two active X chromosomes.
• Primate trophectoderm lineage does not undergo imprinted paternal XCI, highlighting species-specific epigenetic regulation.