Expression reduction of biallelically transcribed X-linked genes during the human female preimplantation development

Our previous single-cell RNA-seq data from human preimplantation embryos showed that female X-chromosome mRNA levels become partly dose compensated during the timespan between zygotic genome activation (ZGA) and implantation. At the same time, XIST RNA is expressed from, and forms clouds in proximity to, both X-chromosome copies and biallelic expression of other X-linked genes persists. We proposed that X-chromosome transcription is transiently lowered on both alleles before X-chromosome inactivation (XCI) takes place. This notion was recently challenged in a reanalysis performed by Moreira de Mello et al, claiming to provide evidence against biallelic expression dampening and that instead proper XCI was responsible for the observed dosage compensation. Here we have addressed this reanalysis and highlighted methodological issues, and we conclude a current lack of evidence against biallelic X-chromosome dampening.