AI Article Synopsis

  • In mammals, females have two X chromosomes, but one is silenced to balance dosage between sexes, with recent research showing that the active X chromosome (Xa) is upregulated during mouse embryonic development.
  • The study explores whether reactivating the inactive X chromosome (Xi) affects Xa upregulation in various cell types, finding a correlation in some contexts like mouse embryonic epiblasts and stem cells, but not in germ cells.
  • Additionally, partial reactivation of Xi in certain cells like mouse extra-embryonic endoderm stem cells and human B cells doesn't lead to loss of Xa upregulation, leading to a new mathematical model for how both X chromosomes are coordinated in transcription.

Article Abstract

In mammals, X chromosome dosage is balanced between sexes through the silencing of one X chromosome in females. Recent single-cell RNA sequencing analysis demonstrated that the inactivation of the X chromosome is accompanied by the upregulation of the active X chromosome (Xa) during mouse embryogenesis. Here, we have investigated if the reactivation of inactive-X (Xi) leads to the loss of Xa upregulation in different cellular or developmental contexts. We find that while Xi reactivation and loss of Xa upregulation are tightly coupled in mouse embryonic epiblast and induced pluripotent stem cells, that is not the case in germ cells. Moreover, we demonstrate that partial reactivation of Xi in mouse extra-embryonic endoderm stem cells and human B cells does not result in the loss of Xa upregulation. Finally, we have established a mathematical model for the transcriptional coordination of two X chromosomes. Together, we conclude that the reactivation of Xi is not always synchronized with the loss of Xa upregulation.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589478PMC
http://dx.doi.org/10.1016/j.stemcr.2024.10.001DOI Listing

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