Imprinted X-chromosome inactivation impacts primitive endoderm differentiation in mouse blastocysts

FEBS Lett. 2020 Mar;594(5):913-923. doi: 10.1002/1873-3468.13676. Epub 2019 Nov 25.

Abstract

Epigenetic and transcriptome alterations are essential for lineage specification, represented by imprinted X-chromosome inactivation (iXCI) in female mouse preimplantation embryos. However, how various factors affect transcriptome states and lineage commitment remains unclear. We found that in vitro culture duration strongly influences transcriptional variation compared to iXCI loss. Single-cell analysis of the inner cell mass (ICM) for major transcription and epigenomic factors revealed that sex-specific differences in expression are diminished by loss of iXCI in the primitive endoderm (PrE) but not in the epiblast. Females had a higher proportion of ICM compared to that in males, and PrE development was affected by iXCI states in female embryos. Our findings provide insight into sex differences and iXCI function in lineage specification.

Keywords: imprinted X-chromosome inactivation; lineage specification; sex difference.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blastocyst / chemistry
  • Blastocyst / cytology*
  • Cell Culture Techniques
  • Cell Differentiation
  • Cell Lineage
  • Cells, Cultured
  • Chromosomes, Mammalian / genetics
  • Endoderm / chemistry
  • Endoderm / cytology*
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation
  • Genomic Imprinting
  • Male
  • Mice
  • RNA, Long Noncoding / genetics*
  • Sequence Analysis, RNA / methods
  • Single-Cell Analysis / methods
  • X Chromosome Inactivation

Substances

  • RNA, Long Noncoding
  • XIST non-coding RNA