Female naïve human pluripotent stem cells carry X chromosomes with Xa-like and Xi-like folding conformations

Sci Adv. 2023 Aug 4;9(31):eadf2245. doi: 10.1126/sciadv.adf2245. Epub 2023 Aug 4.

Abstract

Three-dimensional (3D) genomics shows immense promise for studying X chromosome inactivation (XCI) by interrogating changes to the X chromosomes' 3D states. Here, we sought to characterize the 3D state of the X chromosome in naïve and primed human pluripotent stem cells (hPSCs). Using chromatin tracing, we analyzed X chromosome folding conformations in these cells with megabase genomic resolution. X chromosomes in female naïve hPSCs exhibit folding conformations similar to the active X chromosome (Xa) and the inactive X chromosome (Xi) in somatic cells. However, naïve X chromosomes do not exhibit the chromatin compaction typically associated with these somatic X chromosome states. In H7 naïve human embryonic stem cells, XIST accumulation observed on damaged X chromosomes demonstrates the potential for naïve hPSCs to activate XCI-related mechanisms. Overall, our findings provide insight into the X chromosome status of naïve hPSCs with a single-chromosome resolution and are critical in understanding the unique epigenetic regulation in early embryonic cells.

MeSH terms

  • Chromatin / genetics
  • Chromosomes, Human, X / genetics
  • Epigenesis, Genetic
  • Female
  • Humans
  • Pluripotent Stem Cells*
  • RNA, Long Noncoding* / genetics

Substances

  • RNA, Long Noncoding
  • Chromatin