The X-chromosome dosage compensation program during the development of cynomolgus monkeys

X-chromosome dosage compensation ensures balanced gene dosage between the X chromosome and autosomes and between the sexes, involving divergent mechanisms among mammals. We elucidated a distinct mechanism for X-chromosome inactivation (XCI) in cynomolgus monkeys, a model for human development. The trophectoderm and cytotrophoblast acquire XCI around implantation through an active intermediate bearing repressive modifications and compacted structure, whereas the amnion, epiblast, and hypoblast maintain such an intermediate protractedly, attaining XCI by a week after implantation. Males achieve X-chromosome up-regulation (XCU) progressively, whereas females show XCU coincidentally with XCI, both establishing the X:autosome dosage compensation by 1 week after implantation. Conversely, primordial germ cells undergo X-chromosome reactivation by reversing the XCI pathway early during their development. Our findings establish a foundation for clarifying the dosage compensation mechanisms in primates, including humans. Overall design: Single cell transcriptome analysis of cynomolgus monkey embryo using SC3-seq technology.

X染色体剂量补偿（X-chromosome dosage compensation）可维持X染色体与常染色体间以及不同性别间的基因剂量平衡，其调控机制在哺乳动物中存在显著分化。本研究阐明了作为人类发育模型的食蟹猴中一种独特的X染色体失活（X-chromosome inactivation，XCI）机制。滋养外胚层与细胞滋养层在着床阶段前后，通过携带抑制性修饰且结构致密的活性中间态完成X染色体失活；而羊膜、上胚层及下胚层则较长时间维持该中间态，并于着床后1周内实现XCI。雄性个体逐步完成X染色体上调（X-chromosome up-regulation，XCU），雌性个体的XCU则与XCI同步发生，二者均在着床后1周内建立起X染色体与常染色体的剂量补偿平衡。与之相反，原始生殖细胞在发育早期通过逆转XCI通路实现X染色体再激活。本研究结果为阐明包括人类在内的灵长类动物剂量补偿机制奠定了重要基础。实验整体设计：采用SC3-seq技术对食蟹猴胚胎进行单细胞转录组分析。