Marsupials are a powerful comparative model system with which to understand mammalian biology. Studies on marsupials have provided insights into genome and transcriptome evolution, genomic imprinting, sex determination, neuroregeneration and cancer. Marsupials also exhibit unusual embryonic characteristics. Implantation is later and gestation shorter than in eutherian mammals such as mice and humans. Furthermore, X-chromosome inactivation is carried out not by Xist, as in eutherians, but by another non-coding RNA called RSX. We have recently performed the first single-cell RNA-sequencing analysis of embryogenesis and X-chromosome inactivation in a marsupial, the grey short-tailed opossum Monodelphis domestica. This analysis has revealed fascinating insight into the evolution of lineage specifiers and X-dosage compensation. I will discuss the relevance of our findings to our understanding of early development, stem cell biology and sex chromosome evolution.