Concurrent X chromosome inactivation and upregulation during non-human primate preimplantation development revealed by single-cell RNA-sequencing

Abstract

In mammals, dosage compensation of X-linked gene expression between males and females is achieved by inactivation of a single X chromosome in females, while upregulation of the single active X in males and females leads to X:autosome dosage balance. Studies in human embryos revealed that random X chromosome inactivation starts at the preimplantation stage and is not complete by day 12 of development. Alternatively, others proposed that dosage compensation in human preimplantation embryos is achieved by dampening expression from the two X chromosomes in females. Here, we characterize X-linked dosage compensation in another primate, the marmoset (Callithrix jacchus). Analyzing scRNA-seq data from preimplantation embryos, we detected upregulation of XIST at the morula stage, where female embryos presented a significantly higher expression of XIST than males. Moreover, we show an increase of X-linked monoallelically expressed genes in female embryos between the morula and late blastocyst stages, indicative of XCI. Nevertheless, dosage compensation was not achieved by the late blastocyst stage. Finally, we show that X:autosome dosage compensation is achieved at the 8-cell stage, and demonstrate that X chromosome dampening in females does not take place in the marmoset. Our work contributes to the elucidation of primate X-linked dosage compensation.

Single-cell RNA sequencing reveals the follicle microenvironment of patients with premature ovarian insufficiency

“…The expression of KCNQ1OT1, which is also involved in DNA methylation, is also reported to be signi cantly reduced in vitri ed oocytes [33], suggesting KCNQ1OT1 may be involved in the regulation of ovarian function. Using scRNA-seq data from preimplantation embryos, Cidral et al [34] demonstrated that XIST is upregulated at the morula stage and that its expression is higher in female embryos than in male embryos. Moreover, we nd that the DEGs identi ed in granulosa cells 6 from old individuals and POI patients when compared with the normal group, were all enriched in the phagosome and antigen processing and presentation pathways.…”

Enhanced chromatin accessibility contributes to X chromosome dosage compensation in mammals

“…In addition to XCI, both sexes upregulate the remaining active X chromosome (Xa), in a process known as X chromosome upregulation (XCU), which resolves dosage imbalance between the sole Xa and diploid autosomal gene expression [15][16][17][18][19][20][21]. XCU has been reported in several placental mammals including mice [18,22], marmosets (non-human primates) [23], and humans [18], and in nonplacental mammals such as marsupials [14]. Despite advances, the molecular processes underlying the evolution of XCU in mammals remain unclear.…”